Name	Lung cancer
ICD	ICD-11: 2C25

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	YTHDF2 directly binds to the m6A modification site of 6-phosphogluconate dehydrogenase, decarboxylating (6PGD/PGD) three prime untranslated region (3'-UTR) to promote 6PGD mRNA translation in lung cancer cells.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Pentose phosphate pathway			hsa00030
Cell Process	Cell growth
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	HEK293T	Normal	Homo sapiens	CVCL_0063

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	CBLL1 was frequently upregulated in non-small lung cancer (NSCLC) tissues compared to the adjacent nontumor tissues. CBLL1 knockdown inhibited cell invasion via increased E-cadherin protein expression, and decreased expression of 72 kDa type IV collagenase (MMP2) and MMP9 in NSCLC cell lines.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	E3 ubiquitin-protein ligase Hakai (CBLL1)		WRITER	Regulator Info
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-Aldo-keto reductase family 1 member C1 (AKR1C1) axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 106 p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	Alpha-enolase (ENO1) positively correlated with METTL3 and global m6A levels, and negatively correlated with ALKBH5 in human Lung adenocarcinoma(LUAD). In addition, m6A-dependent elevation of ENO1 was associated with LUAD progression.
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Carbon metabolism			hsa01200
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	NCI-H441	Lung papillary adenocarcinoma	Homo sapiens	CVCL_1561
	NCI-H292	Lung mucoepidermoid carcinoma	Homo sapiens	CVCL_0455
	NCI-H2030	Lung adenocarcinoma	Homo sapiens	CVCL_1517
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	3LL	Malignant tumors of the mouse pulmonary system	Mus musculus	CVCL_5653
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	Calu-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0608
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A-427	Lung adenocarcinoma	Homo sapiens	CVCL_1055
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	KP and Mettl3-/- mice were bred to generate KPM-/- mice. Afterwards, the KP and KPM-/- mice were intranasally infected under anesthesia with adeno-associated virus type 5 (AAV5) expressing Cre to initiate lung tumorigenesis along with ALKBH5-expressing AAV5 or Empty AAV5 to generate KPE, KPA, KPEM-/- and KPAM-/- spontaneous LUAD mouse models. For generation of LLC-based intra-pulmonary tumor mouse models, 1 × 107 LLC cells were injected into C57BL/6 mice via the tail vein.For cell-derived xenograft (CDX) mouse models, 1.0 × 107 H1299 or 1.5 × 107 H1975 cells were subcutaneously injected into 4-6-week-old athymic nude mice. The tumors were monitored at indicated time points and isolated for further analysis after sacrifice.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	Alpha-enolase (ENO1) positively correlated with METTL3 and global m6A levels, and negatively correlated with ALKBH5 in human Lung adenocarcinoma(LUAD). In addition, m6A-dependent elevation of ENO1 was associated with LUAD progression.
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Carbon metabolism			hsa01200
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	NCI-H441	Lung papillary adenocarcinoma	Homo sapiens	CVCL_1561
	NCI-H292	Lung mucoepidermoid carcinoma	Homo sapiens	CVCL_0455
	NCI-H2030	Lung adenocarcinoma	Homo sapiens	CVCL_1517
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	3LL	Malignant tumors of the mouse pulmonary system	Mus musculus	CVCL_5653
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	Calu-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0608
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A-427	Lung adenocarcinoma	Homo sapiens	CVCL_1055
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	KP and Mettl3-/- mice were bred to generate KPM-/- mice. Afterwards, the KP and KPM-/- mice were intranasally infected under anesthesia with adeno-associated virus type 5 (AAV5) expressing Cre to initiate lung tumorigenesis along with ALKBH5-expressing AAV5 or Empty AAV5 to generate KPE, KPA, KPEM-/- and KPAM-/- spontaneous LUAD mouse models. For generation of LLC-based intra-pulmonary tumor mouse models, 1 × 107 LLC cells were injected into C57BL/6 mice via the tail vein.For cell-derived xenograft (CDX) mouse models, 1.0 × 107 H1299 or 1.5 × 107 H1975 cells were subcutaneously injected into 4-6-week-old athymic nude mice. The tumors were monitored at indicated time points and isolated for further analysis after sacrifice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	METTL3 regulated cellular growth, survival and migration in non-small cell lung cancer. METTL3 promoted non-small cell lung cancer progression by modulating the level of Apoptosis regulator Bcl-2 (BCL2).
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	The mice were housed with filtered air, 12 h light/dark cycle, constant temperature (25℃), relative humidity (50±5%) and free access to food and water. In order to establish a human NSCLC xenograft model, 5×106 H1299, sh-METTL3-H1299 and METTL3 stably overexpressed H1299 cells (2×106 per mouse) were subcutaneously injected into mice. Tumor growth was observed daily. Tumor volume was calculated as follows: 0.5× (length × width2). At 24 days post-inoculation, the maximum diameter exhibited by a single subcutaneous tumor was 15 mm and mice were anesthetized by intraperitoneal administration of sodium pentobarbital (50 mg/kg), then sacrificed by cervical dislocation.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	Not only FTO knockdown enhanced the gefitinib sensitivity of GR cells but also FTO reduction in donor exosomes alleviated the acquired resistance of recipient non-small cell lung cancer PC9 cells. FTO/YTHDF2/ATP-binding cassette sub-family C member 10 (ABCC10) axis played a role in intercellular transmission of GR cell-derived exosome-mediated gefitinib resistance.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	ABC transporters			hsa02010
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
In-vivo Model	Mice were randomized into three groups (n = 7/group), 1 × 107 PC9 cells absorbed exosomes were subcutaneously injected into the Bilateral groin of mice. Treatment began 1 week following injection, the mice were intraperitoneally injected with gefitinib (30 mg/kg/day).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	Not only FTO knockdown enhanced the gefitinib sensitivity of GR cells but also FTO reduction in donor exosomes alleviated the acquired resistance of recipient non-small cell lung cancer PC9 cells. FTO/YTHDF2/ATP-binding cassette sub-family C member 10 (ABCC10) axis played a role in intercellular transmission of GR cell-derived exosome-mediated gefitinib resistance.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	ABC transporters			hsa02010
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
In-vivo Model	Mice were randomized into three groups (n = 7/group), 1 × 107 PC9 cells absorbed exosomes were subcutaneously injected into the Bilateral groin of mice. Treatment began 1 week following injection, the mice were intraperitoneally injected with gefitinib (30 mg/kg/day).

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as Autophagy protein 5 (ATG5), ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Chloroquine		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as Autophagy protein 5 (ATG5), ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as Autophagy protein 5 (ATG5), ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Beta-Elemen		Phase 3	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	In lung squamous cell carcinoma, seven m6A-related autophagy genes were screened to construct a prognostic model: Caspase-4 (CASP4), CDKN1A, DLC1, ITGB1, PINK1, TP63, and EIF4EBP1.
Responsed Disease	Lung squamous cell carcinoma [ICD-11: 2C25.2]
Pathway Response	Autophagy			hsa04140
Cell Process	Cell proliferation and metastasis
	Cell autophagy

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[9]
Response Summary	ECs transmitted miR-376c into NSCLC cells through Evs, and inhibited the intracellular YTHDF1 expression and the Wnt/Catenin beta-1 (CTNNB1/Beta-catenin) pathway activation. YTHDF1 overexpression reversed the inhibitory role of miR-376c released by EC-Evs in non-small cell lung cancer cells.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell invasion
	Cell migration
	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-1650 (Non-Small Cell Lung Cancer Cells)
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H358	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1559

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	Knockdown of Cellular tumor antigen p53 (TP53/p53) or inhibition of p53's transcriptional activity by addition of its specific inhibitor PFT-Alpha decreased expression of ALKBH5 and Cancer stem cells' malignancies, the pivotal role of ALKBH5 in Cancer stem cells derived from nonsmall-cell lung cancer and highlight the regulatory function of the p53/ALKBH5 axis in modulating CSC progression. p53 transcriptionally regulates PRRX1, which is consistent with our previous report.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	Cells at 1 × 106 were subcutaneously injected into the mice similarly to nude mice. Twenty-eight days later, grafted tumors were collected and morphologically analyzed.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[11]
Response Summary	Complex I-AGGG (NDUFB2) interacts with IGF2BP1/2/3 in NSCLC cells. circNDUFB2 participates in the degradation of IGF2BPs and activation of anti-tumor immunity during NSCLC progression via the modulation of both protein ubiquitination and degradation, as well as cellular immune responses.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Tumour immunology
	Ubiquitination degradation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1703	Lung squamous cell carcinoma	Homo sapiens	CVCL_1490
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	LL/2 (LLC1)	Malignant tumors	Mus musculus	CVCL_4358
In-vivo Model	A549 cells were transfected with the pZW1-FCS-circNDUFB2 plasmid or pZW1-FCS-Vector plasmid, and selected with G418 (800 ug/ml) for 4 weeks, and then 2 × 106 A549 cells were subcutaneously injected into the right flank of each mouse.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of Cyclin-dependent kinase 2 (CDK2), CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 106 p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, Cyclin-dependent kinase 4 (CDK4), p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 106 p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including E2F3, WTAP, CCND1, Cyclin-dependent kinase 4 (CDK4), EGR2, YBX1, and TLX, which were associated with lung cancers.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Cell Process	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	HBE (Human bronchial epithelial cell line)
	LTEP-a2	Endocervical adenocarcinoma	Homo sapiens	CVCL_6929
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including E2F3, WTAP, CCND1, Cyclin-dependent kinase 4 (CDK4), EGR2, YBX1, and TLX, which were associated with lung cancers.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Cell Process	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	HBE (Human bronchial epithelial cell line)
	LTEP-a2	Endocervical adenocarcinoma	Homo sapiens	CVCL_6929
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	In lung squamous cell carcinoma, seven m6A-related autophagy genes were screened to construct a prognostic model: CASP4, Cyclin-dependent kinase inhibitor 1 (CDKN1A), DLC1, ITGB1, PINK1, TP63, and EIF4EBP1.
Responsed Disease	Lung squamous cell carcinoma [ICD-11: 2C25.2]
Pathway Response	Autophagy			hsa04140
Cell Process	Cell proliferation and metastasis
	Cell autophagy
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[13]
Response Summary	The expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A) or TIMP3 was increased by ALKBH5 knockdown. In conclusions, the ALKBH5-IGF2BPs axis promotes cell proliferation and tumorigenicity, which in turn causes the unfavorable prognosis of NSCLC.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Arrest cell cycle at G1 phase
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H2087	Lung adenocarcinoma	Homo sapiens	CVCL_1524
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	ABC-1	Lung adenocarcinoma	Homo sapiens	CVCL_1066
	NCI-H358	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1559
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	HEK293	Normal	Homo sapiens	CVCL_0045
	PC-3 [Human lung carcinoma]	Lung adenocarcinoma	Homo sapiens	CVCL_S982
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	RERF-LC-MS	Lung adenocarcinoma	Homo sapiens	CVCL_1655
	HLC-1	Lung adenocarcinoma	Homo sapiens	CVCL_5529
	LC-2/ad	Lung adenocarcinoma	Homo sapiens	CVCL_1373

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, Cyclin-dependent kinase inhibitor 1B (CDKN1B/p27), and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 106 p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[14]
Response Summary	METTL3-mediated m-6A modification could stabilize Cystine/glutamate transporter (SLC7A11) mRNA and promote its translation, thus promoting LUAD cell proliferation and inhibiting cell ferroptosis, a novel form of programmed cell death.
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Ferroptosis			hsa04216
Cell Process	Ferroptosis
In-vitro Model	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H322	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1556
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	For the subcutaneous xenograft model, PC9 cells stably transfected with METTL3 knockdown (shMETTL3) or negative control (shNC) shRNA (5 × 106 cells per mouse, n = 6) were suspended in 200 uL PBS with 50% Matrigel matrix (Corning, USA, 354234) and then injected into one side of the axilla of nude mice.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[15]
Response Summary	YTHDC2 destabilized Cystine/glutamate transporter (SLC7A11) mRNA in an m6A-dependent manner because YTHDC2 preferentially bound to m6A-modified SLC7A11 mRNA and thereafter promoted its decay. the promotion of cystine uptake via the suppression of YTHDC2 is critical for LUAD tumorigenesis
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulator	YTH domain-containing protein 2 (YTHDC2)		READER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	NCI-H441	Lung papillary adenocarcinoma	Homo sapiens	CVCL_1561
	NCI-H292	Lung mucoepidermoid carcinoma	Homo sapiens	CVCL_0455
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	Calu-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0608
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[16]
Response Summary	Cigarette smoking induced aberrant N6-methyladenosine modification of Death-associated protein kinase 2 (DAPK2), which resulted in decreased DAPK2 mRNA stability and expression of its mRNA and protein. This modification was mediated by the m6A "writer" METTL3 and the m6A "reader" YTHDF2. BAY 11-7085, a NF-Kappa-B signaling selective inhibitor, was shown to efficiently suppressed downregulation of DAPK2-induced oncogenic phenotypes of NSCLC cells.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	The nude mice were maintained under pathogen-free conditions and kept under timed lighting conditions mandated by the committee with food and water provided ad libitum. For xenograft experiments, nude mice were injected subcutaneously with 5 × 106 cells resuspended in 0.1 mL PBS. When a tumor was palpable, it was measured every 3 days.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[16]
Response Summary	Cigarette smoking induced aberrant N6-methyladenosine modification of Death-associated protein kinase 2 (DAPK2), which resulted in decreased DAPK2 mRNA stability and expression of its mRNA and protein. This modification was mediated by the m6A "writer" METTL3 and the m6A "reader" YTHDF2. BAY 11-7085, a NF-Kappa-B signaling selective inhibitor, was shown to efficiently suppressed downregulation of DAPK2-induced oncogenic phenotypes of NSCLC cells.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	The nude mice were maintained under pathogen-free conditions and kept under timed lighting conditions mandated by the committee with food and water provided ad libitum. For xenograft experiments, nude mice were injected subcutaneously with 5 × 106 cells resuspended in 0.1 mL PBS. When a tumor was palpable, it was measured every 3 days.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[17]
Response Summary	High expression of KIAA1429 was testified in patients with non-small cell lung cancer and predicted worse prognosis in patients. KIAA1429-guided m6A modifications promoted NSCLC progression via m6A-dependent degradation of Death-associated protein kinase 3 (DAPK3) mRNA.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including E2F3, WTAP, CCND1, CDK4, E3 SUMO-protein ligase EGR2 (EGR2), YBX1, and TLX, which were associated with lung cancers.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Cell Process	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	HBE (Human bronchial epithelial cell line)
	LTEP-a2	Endocervical adenocarcinoma	Homo sapiens	CVCL_6929
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including E2F3, WTAP, CCND1, CDK4, E3 SUMO-protein ligase EGR2 (EGR2), YBX1, and TLX, which were associated with lung cancers.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Cell Process	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	HBE (Human bronchial epithelial cell line)
	LTEP-a2	Endocervical adenocarcinoma	Homo sapiens	CVCL_6929
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[18]
Response Summary	METTL3 positively regulates F-box/WD repeat-containing protein 7 (FBXW7) expression and confirm the tumor-suppressive role of m6A-modified FBXW7, thus providing insight into its epigenetic regulatory mechanisms in lung adenocarcinoma initiation and development.
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Cell Process	RNA stability
	Cell apoptosis
In-vitro Model	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	The mice were randomly divided into groups before subcutaneous injection with cells (107) suspended in 200 uL of phosphate-buffered saline. Tumors were measured on day 7 and then once every 7 days until 28 days after injection.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[19]
Response Summary	LCAT3 upregulation is attributable to N6-methyladenosine (m6A) modification mediated by methyltransferase like 3 (METTL3), leading to LCAT3 stabilization. LCAT3 as a novel oncogenic lncRNA in the lung, and validated the LCAT3-Far upstream element-binding protein 1 (FUBP1)-MYC axis as a potential therapeutic target for lung adenocarcinomas.
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0608
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HOP-62	Lung adenocarcinoma	Homo sapiens	CVCL_1285
In-vivo Model	For the in vivo tumorigenicity assay, female BALB/c nude mice (ages 4-5 weeks) were randomly divided into two groups (n = 6/group). Calu1 cells (4 × 106) that had been stably transfected with sh-LCAT3 or scramble were implanted subcutaneously into the nude mice. Tumor growth was measured after one week, and tumor volumes were calculated with the following formula: Volume (cm3) = (length × width2)/2. After four weeks, the mice were euthanized, and the tumors were collected and weighed. For the in vivo tumor invasion assay, 1.2 × 106 scramble or shLCAT3 cells were injected intravenously into the tail vein of nude mice (n = 6/group). 1.5 mg luciferin (Gold Biotech, St Louis, MO, USA) was administered once a week for 4 weeks, to monitor metastases using an IVIS@ Lumina II system (Caliper Life Sciences, Hopkinton, MA, USA).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[20]
Response Summary	m6A demethylase ALKBH5 affects the proliferation and invasion of lung adenocarcinoma cells under IH by downregulating m6A modification on Forkhead box protein M1 (FOXM1) mRNA and by promoting FOXM1 expression.high FOXM1 expression was associated with cisplatin-based chemotherapy resistance and poor prognosis
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Cellular senescence			hsa04218
Cell Process	Cell proliferation and invasion
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H522	Lung adenocarcinoma	Homo sapiens	CVCL_1567
In-vivo Model	1 × 107 A549 cells were subcutaneously implanted into 4-week-old NOD/SCID mice.

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and G1/S-specific cyclin-D1 (CCND1), and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 106 p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including E2F3, WTAP, G1/S-specific cyclin-D1 (CCND1), CDK4, EGR2, YBX1, and TLX, which were associated with lung cancers.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Cell Process	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	HBE (Human bronchial epithelial cell line)
	LTEP-a2	Endocervical adenocarcinoma	Homo sapiens	CVCL_6929
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including E2F3, WTAP, G1/S-specific cyclin-D1 (CCND1), CDK4, EGR2, YBX1, and TLX, which were associated with lung cancers.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Cell Process	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	HBE (Human bronchial epithelial cell line)
	LTEP-a2	Endocervical adenocarcinoma	Homo sapiens	CVCL_6929
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[21]
Response Summary	Chidamide could decrease Hepatocyte growth factor receptor (c-Met/MET) expression by inhibiting mRNA N6-methyladenosine (m6A) modification through the downregulation of METTL3 and WTAP expression, subsequently increasing the crizotinib sensitivity of NSCLC cells in a c-MET-/HGF-dependent manner.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Crizotinib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	EGFR tyrosine kinase inhibitor resistance			hsa01521
In-vitro Model	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	NCI-H661	Lung large cell carcinoma	Homo sapiens	CVCL_1577
	NCI-H596	Lung adenosquamous carcinoma	Homo sapiens	CVCL_1571
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H358	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1559
	NCI-H292	Lung mucoepidermoid carcinoma	Homo sapiens	CVCL_0455
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1395	Lung adenocarcinoma	Homo sapiens	CVCL_1467
	EBC-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_2891
	Calu-3	Lung adenocarcinoma	Homo sapiens	CVCL_0609
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	HCC827 (3×106) cells suspended in 100 uL of PBS were injected into the left inguen of female Balb/c nude mice (body weight 18-20 g; age 6 weeks; Beijing Huafukang Bioscience Co., Inc.). When the tumor volumes reached 50-100 mm3 on the 10th posttransplantation day, the mice were randomized into four groups (10 mice per group) and were intragastrically administered vehicle (normal saline), crizotinib (25 mg/kg body weight), chidamide (5 mg/kg), or the combination of the two drugs daily for 21 days. The tumor volumes and body weights of the mice were measured every 3 days.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[21]
Response Summary	Chidamide could decrease Hepatocyte growth factor receptor (c-Met/MET) expression by inhibiting mRNA N6-methyladenosine (m6A) modification through the downregulation of METTL3 and WTAP expression, subsequently increasing the crizotinib sensitivity of NSCLC cells in a c-MET-/HGF-dependent manner.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Crizotinib		Approved	Drug Info
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	EGFR tyrosine kinase inhibitor resistance			hsa01521
In-vitro Model	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	NCI-H661	Lung large cell carcinoma	Homo sapiens	CVCL_1577
	NCI-H596	Lung adenosquamous carcinoma	Homo sapiens	CVCL_1571
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H358	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1559
	NCI-H292	Lung mucoepidermoid carcinoma	Homo sapiens	CVCL_0455
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1395	Lung adenocarcinoma	Homo sapiens	CVCL_1467
	EBC-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_2891
	Calu-3	Lung adenocarcinoma	Homo sapiens	CVCL_0609
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	HCC827 (3×106) cells suspended in 100 uL of PBS were injected into the left inguen of female Balb/c nude mice (body weight 18-20 g; age 6 weeks; Beijing Huafukang Bioscience Co., Inc.). When the tumor volumes reached 50-100 mm3 on the 10th posttransplantation day, the mice were randomized into four groups (10 mice per group) and were intragastrically administered vehicle (normal saline), crizotinib (25 mg/kg body weight), chidamide (5 mg/kg), or the combination of the two drugs daily for 21 days. The tumor volumes and body weights of the mice were measured every 3 days.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[22]
Response Summary	METTL3 combines with Hepatocyte growth factor receptor (c-Met/MET) and causes the PI3K/AKT signalling pathway to be manipulated, which affects the sensitivity of lung cancer cells to gefitinib. METTL3 knockdown promotes apoptosis and inhibits proliferation of lung cancer cells.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	NCI-H3255	Lung adenocarcinoma	Homo sapiens	CVCL_6831

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[23]
Response Summary	Simvastatin induces METTL3 down-regulation in lung cancer tissues, which further influences EMT via m6A modification on Histone-lysine N-methyltransferase EZH2 (EZH2) mRNA and thus inhibits the malignant progression of lung cancer.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[24]
Response Summary	m6A methyltransferase KIAA1429 was highly expressed in gefitinib-resistant NSCLC cells (PC9-GR), tissues, and closely related to unfavorable survival. KIAA1429 plays essential oncogenic roles in NSCLC gefitinib resistance, which provided a feasible therapeutic target for NSCLC.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	NHBE (Normal bronchial epithelial cells)
In-vivo Model	PC9-GR cells stably infected with KIAA1429-targeting shRNA and control were suspended in 100 uL of PBS with Matrigel matrix (BD Biosciences). Then, cells were injected into one of the flanks of BALB/c nude mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[25]
Response Summary	overexpression of IGFBP3 induced apoptosis and enhanced cisplatin response in vitro and confirmed that the suppression is in part by blocking Insulin-like growth factor I (IGF1) signaling. IGFBP3 is effective in lung cancer cells with high IGF1 signaling activity and imply that relevant biomarkers are essential in selecting lung cancer patients for IGF1-targeted therapy.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	Insulin-like growth factor-binding protein 3 (IGFBP3)		READER	Regulator Info
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	Cell apoptosis
In-vitro Model	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	HCC2429	Lung non-small cell carcinoma	Homo sapiens	CVCL_5132
In-vivo Model	Paired littermates of F2 (Igfbp3+/+:KrasG12D/+ and Igfbp3-/-:KrasG12D/+) were sacrificed ranging from ages 4 to 7 months. After preliminary analysis of F2 mice, we sacrificed 5-month-old Igfbp3+/+:KrasG12D/+ and Igfbp3-/-KrasG12D/+ mice that had been backcrossed to S129 background for representative analysis. The lung tissue was immediately removed after the mice were sacrificed and visible pleural nodules were counted directly.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	In lung squamous cell carcinoma, seven m6A-related autophagy genes were screened to construct a prognostic model: CASP4, CDKN1A, DLC1, Integrin beta-1 (ITGB1), PINK1, TP63, and EIF4EBP1.
Responsed Disease	Lung squamous cell carcinoma [ICD-11: 2C25.2]
Pathway Response	Autophagy			hsa04140
Cell Process	Cell proliferation and metastasis
	Cell autophagy

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Kelch-like ECH-associated protein 1 (KEAP1)-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 106 p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[26]
Response Summary	miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor Krueppel-like factor 4 (KLF4). miR-1915-3p function as a tumor suppressor by targeting SET and has an anti-metastatic therapeutic potential for lung cancer treatment.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	TNF signaling pathway			hsa04668
Cell Process	Cell migration
	Cell invasion
	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[26]
Response Summary	miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor Krueppel-like factor 4 (KLF4). miR-1915-3p function as a tumor suppressor by targeting SET and has an anti-metastatic therapeutic potential for lung cancer treatment.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	TNF signaling pathway			hsa04668
Cell Process	Cell migration
	Cell invasion
	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[27]
Response Summary	NNK is a Group 1 human carcinogen, as classified by the International Agency for Research of Cancer (IARC), and plays a significant role in lung carcinogenesis. However IGF2BP1 is involved in the NNK-induced malignant transformation of Beas-2B cells, via m6A modification.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Pathway Response	Chemical carcinogenesis - DNA adducts			hsa05204
Cell Process	Malignant transformation
In-vitro Model	BEAS-2B	Normal	Homo sapiens	CVCL_0168
In-vivo Model	Twenty 5-week-old male nude mice were randomly divided into two groups and injected with either 2B-NNK or 2B-C cells. Tumor growth was measured every 3 days.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	CBLL1 was frequently upregulated in non-small lung cancer (NSCLC) tissues compared to the adjacent nontumor tissues. CBLL1 knockdown inhibited cell invasion via increased E-cadherin protein expression, and decreased expression of MMP2 and Matrix metalloproteinase-9 (MMP9) in NSCLC cell lines.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	E3 ubiquitin-protein ligase Hakai (CBLL1)		WRITER	Regulator Info
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[28]
Response Summary	ALKBH5 repress Metalloproteinase inhibitor 3 (TIMP3) transcript stability, thereby inhibiting TIMP3 translational production.the present research confirmed the ALKBH5/TIMP3 pathway in the non-small cell lung cancer(NSCLC) oncogenesis progress, providing a novel insight for the epitranscriptome and potential therapeutic target for NSCLC.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Down regulation
Cell Process	RNA stability
	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NHBE (Normal bronchial epithelial cells)
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630
In-vivo Model	2 × 106 A549 cells stably transfected with shRNA-ALKBH5 were injected into the flank of male athymic BALB/c nude mice (4-5 weeks old, 10 mice).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[13]
Response Summary	The expression of CDKN1A (p21) or Metalloproteinase inhibitor 3 (TIMP3) was increased by ALKBH5 knockdown. In conclusions, the ALKBH5-IGF2BPs axis promotes cell proliferation and tumorigenicity, which in turn causes the unfavorable prognosis of NSCLC.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Arrest cell cycle at G1 phase
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H2087	Lung adenocarcinoma	Homo sapiens	CVCL_1524
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	ABC-1	Lung adenocarcinoma	Homo sapiens	CVCL_1066
	NCI-H358	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1559
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	HEK293	Normal	Homo sapiens	CVCL_0045
	PC-3 [Human lung carcinoma]	Lung adenocarcinoma	Homo sapiens	CVCL_S982
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	RERF-LC-MS	Lung adenocarcinoma	Homo sapiens	CVCL_1655
	HLC-1	Lung adenocarcinoma	Homo sapiens	CVCL_5529
	LC-2/ad	Lung adenocarcinoma	Homo sapiens	CVCL_1373

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B/LC3B-II). beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Chloroquine		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B/LC3B-II). beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B/LC3B-II). beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Beta-Elemen		Phase 3	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[29]
Response Summary	YTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the FAM83D-TGFbeta1-Mothers against decapentaplegic homolog 2 (SMAD2) pathway, which will play an important role in lung cancer metastasis.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[29]
Response Summary	YTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the FAM83D-TGFbeta1-Mothers against decapentaplegic homolog 3 (SMAD3) pathway, which will play an important role in lung cancer metastasis.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[30]
Response Summary	ALKBH5 weakens YTHDF1/3-mediated TGF-Beta-R2 and Mothers against decapentaplegic homolog 3 (SMAD3) mRNA stabilization, and abolishes YTHDF2-mediated SMAD6 mRNA degradation, supporting the notion that ALKBH5 inhibits TGF-Beta-induced EMT and invasion of NSCLC cells via YTHD1/2/3-mediated mechanism.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Down regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	The mice were divided into control group and ALKBH5-overexpressing group (9 mice per group). ALKBH5-overexpressing and control A549 cells (3 × 106 cells/mouse) in 200 uL PBS were intravenously (i.v.) injected into the lateral tail vein of mice. At every 5th day post-inoculation, TGF-Beta-1 (4 ug/kg body weight) was intraperitoneally (i.p.) injected to promote tumor cell metastasis. Eight weeks later, the mice were euthanized, and then their lungs and livers were taken out and fixed in Bouin's solution (Sigma Aldrich, HT101128) or 4% Paraformaldehyde (Beyotime, p0099, Shanghai, China) for macroscopically metastatic nodule analysis.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[30]
Response Summary	ALKBH5 weakens YTHDF1/3-mediated TGF-Beta-R2 and SMAD3 mRNA stabilization, and abolishes YTHDF2-mediated Mothers against decapentaplegic homolog 6 (SMAD6) mRNA degradation, supporting the notion that ALKBH5 inhibits TGF-Beta-induced EMT and invasion of NSCLC cells via YTHD1/2/3-mediated mechanism.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	The mice were divided into control group and ALKBH5-overexpressing group (9 mice per group). ALKBH5-overexpressing and control A549 cells (3 × 106 cells/mouse) in 200 uL PBS were intravenously (i.v.) injected into the lateral tail vein of mice. At every 5th day post-inoculation, TGF-Beta-1 (4 ug/kg body weight) was intraperitoneally (i.p.) injected to promote tumor cell metastasis. Eight weeks later, the mice were euthanized, and then their lungs and livers were taken out and fixed in Bouin's solution (Sigma Aldrich, HT101128) or 4% Paraformaldehyde (Beyotime, p0099, Shanghai, China) for macroscopically metastatic nodule analysis.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[31]
Response Summary	KIAA1429 regulates Mucin-3A (MUC3A) expression through m6A modification to modulate LUAD cells to proliferate, migrate, invade, and induce cell cycle arrest.
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulation	Up regulation
Cell Process	Cell migration
	celCl proliferation
	Cell invasion
In-vitro Model	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	HBE (Human bronchial epithelial cell line)
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	PLA-801D	Lung giant cell carcinoma	Homo sapiens	CVCL_7110

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[32]
Response Summary	Bete-elemene exerted the restrictive impacts on the cell growth of lung cancer in vivo and in vitro through targeting METTL3. Bete-elemene contributed to the augmented PTEN expression via suppressing its m6A modification.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	Four-week-old BALB/c nude mice were randomly divided into three groups: (1) vector group, (2) vector + Bete-elemene group, and (3) Bete-elemene + METTL3 group. Nude mice were raised in an SPF level animal house and were free to eat and drink. Mice in the vector group were subcutaneously injected with lung cancer cells transfected with empty vector and did not receive Bete-elemene administration, and this group was implemented as the negative control. Following establishing orthotopic xenografts by using A549 or H1299 cells transfected with empty vector, mice in the vector + Bete-elemene group underwent intraperitoneal injection with Bete-elemene once a day. For the subcutaneous transplanted model, A549 or H1299 cells transfected with METTL3-overexpressing vector were inoculated into mice from the Bete-elemene + METTL3 group. Then, mice were intraperitoneally administrated with Bete-elemene once a day. Three weeks later, all the animals were euthanized with CO2. Xenografts were removed and weighted after mice were euthanatized.

In total 4 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[19]
Response Summary	LCAT3 upregulation is attributable to N6-methyladenosine (m6A) modification mediated by methyltransferase like 3 (METTL3), leading to LCAT3 stabilization. LCAT3 as a novel oncogenic lncRNA in the lung, and validated the LCAT3-FUBP1-Myc proto-oncogene protein (MYC) axis as a potential therapeutic target for lung adenocarcinomas.
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0608
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HOP-62	Lung adenocarcinoma	Homo sapiens	CVCL_1285
In-vivo Model	For the in vivo tumorigenicity assay, female BALB/c nude mice (ages 4-5 weeks) were randomly divided into two groups (n = 6/group). Calu1 cells (4 × 106) that had been stably transfected with sh-LCAT3 or scramble were implanted subcutaneously into the nude mice. Tumor growth was measured after one week, and tumor volumes were calculated with the following formula: Volume (cm3) = (length × width2)/2. After four weeks, the mice were euthanized, and the tumors were collected and weighed. For the in vivo tumor invasion assay, 1.2 × 106 scramble or shLCAT3 cells were injected intravenously into the tail vein of nude mice (n = 6/group). 1.5 mg luciferin (Gold Biotech, St Louis, MO, USA) was administered once a week for 4 weeks, to monitor metastases using an IVIS@ Lumina II system (Caliper Life Sciences, Hopkinton, MA, USA).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[33]
Response Summary	This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher programmed death-ligand 1 (PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The Myc proto-oncogene protein (MYC) targets, E2 transcription Factor (E2F) targets were significantly enriched.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Pathway Response	p53 signaling pathway			hsa04115
	Central carbon metabolism in cancer			hsa05230
	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[33]
Response Summary	This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher programmed death-ligand 1 (PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The Myc proto-oncogene protein (MYC) targets, E2 transcription Factor (E2F) targets were significantly enriched.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Pathway Response	p53 signaling pathway			hsa04115
	Central carbon metabolism in cancer			hsa05230
	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene				[33]
Response Summary	This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher programmed death-ligand 1 (PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The Myc proto-oncogene protein (MYC) targets, E2 transcription Factor (E2F) targets were significantly enriched.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Pathway Response	p53 signaling pathway			hsa04115
	Central carbon metabolism in cancer			hsa05230
	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[34]
Response Summary	FTO enhanced Myeloid zinc finger 1 (MZF1) expression by reducing m6A levels and mRNA stability in MZF1 mRNA transcript, leading to oncogenic functions. The functional importance of FTO in the tumor progression of LUSC and provides a potential therapeutic target for LUSC treatment.
Responsed Disease	Lung squamous cell carcinoma [ICD-11: 2C25.2]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Cell Process	mRNA stability
In-vitro Model	16HBE14o-	Normal	Homo sapiens	CVCL_0112
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	CHLH-1 (The human squamous lung cancer cell line)
	NCI-H226	Pleural epithelioid mesothelioma	Homo sapiens	CVCL_1544
	CHLH-1 (The human squamous lung cancer cell line)
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nuclear factor erythroid 2-related factor 2 (NFE2L2)-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 106 p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including E2F3, WTAP, CCND1, CDK4, EGR2, YBX1, and Nuclear receptor subfamily 2 group E member 1 (TLX/NR2E1), which were associated with lung cancers.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Cell Process	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	HBE (Human bronchial epithelial cell line)
	LTEP-a2	Endocervical adenocarcinoma	Homo sapiens	CVCL_6929
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including E2F3, WTAP, CCND1, CDK4, EGR2, YBX1, and Nuclear receptor subfamily 2 group E member 1 (TLX/NR2E1), which were associated with lung cancers.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Cell Process	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	HBE (Human bronchial epithelial cell line)
	LTEP-a2	Endocervical adenocarcinoma	Homo sapiens	CVCL_6929
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	Knockdown of p53 or inhibition of p53's transcriptional activity by addition of its specific inhibitor PFT-Alpha decreased expression of ALKBH5 and Cancer stem cells' malignancies, the pivotal role of ALKBH5 in Cancer stem cells derived from nonsmall-cell lung cancer and highlight the regulatory function of the p53/ALKBH5 axis in modulating CSC progression. p53 transcriptionally regulates Paired mesoderm homeobox protein 1 (PRRX1), which is consistent with our previous report.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	Cells at 1 × 106 were subcutaneously injected into the mice similarly to nude mice. Twenty-eight days later, grafted tumors were collected and morphologically analyzed.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	METTL3 regulates the m6A modification to promote the maturation of miR-1246, which targets Paternally-expressed gene 3 protein (PEG3) to participate in occurrence and development of non-small cell lung cancer.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	The 40 nude mice of each large group were classified into 8 small groups (n = 5) and subcutaneously injected with transfected cell suspension in the back (5 × 106 cells/mL/mouse). The length and width of tumors were recorded every 4 days, and the tumor volume = (length × width2)/2. The tumor growth curve was thereby graphed. On the 28th day of injection, mice were euthanized by neck dislocation, and the xenografts were harvested, photographed, and weighed

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[36]
Response Summary	miR-600 inhibited lung cancer via down-regulating METTL3 expression, and knockdown of METTL3 was used as a novel strategy for lung cancer therapy. The PI3-kinase subunit alpha (PI3k/PIK3CA)/Akt pathway is implicated in cell growth and survival and we also observed that knockdown of METTL3 changed the expression and phosphorylation of proteins of PI3K signaling pathway members.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[37]
Response Summary	METTL3-mediated m6 A methylation promotes lung cancer progression via activating PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT/mTOR pathway.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	5 × 106 A549 cells overexpressing METTL3 (Lv-METTL3) or control (Lv-Ctrl) were suspended in 100?uL phosphate-buffered saline (PBS), and were subcutaneously injected into mouse lower right flank. Drug treatment started in the Lv-METTL3 group when the tumour volume reached around 100 mm3. Mice were randomly divided into three groups to receive vehicle, GSK2536771 (30 mg/kg) or rapamycin (1 mg/kg). Drugs were administrated daily through intraperitoneal injection for 18 days. Treatment conditions were chosen as previously reported.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including E2F3, Pre-mRNA-splicing regulator WTAP (WTAP), CCND1, CDK4, EGR2, YBX1, and TLX, which were associated with lung cancers.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Cell Process	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	HBE (Human bronchial epithelial cell line)
	LTEP-a2	Endocervical adenocarcinoma	Homo sapiens	CVCL_6929
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including E2F3, Pre-mRNA-splicing regulator WTAP (WTAP), CCND1, CDK4, EGR2, YBX1, and TLX, which were associated with lung cancers.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Cell Process	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	HBE (Human bronchial epithelial cell line)
	LTEP-a2	Endocervical adenocarcinoma	Homo sapiens	CVCL_6929
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[33]
Response Summary	This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher Programmed cell death 1 ligand 1 (CD274/PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, E2 transcription Factor (E2F) targets were significantly enriched.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Pathway Response	p53 signaling pathway			hsa04115
	Central carbon metabolism in cancer			hsa05230
	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[33]
Response Summary	This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher Programmed cell death 1 ligand 1 (CD274/PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, E2 transcription Factor (E2F) targets were significantly enriched.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Pathway Response	p53 signaling pathway			hsa04115
	Central carbon metabolism in cancer			hsa05230
	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[33]
Response Summary	This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher Programmed cell death 1 ligand 1 (CD274/PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, E2 transcription Factor (E2F) targets were significantly enriched.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Pathway Response	p53 signaling pathway			hsa04115
	Central carbon metabolism in cancer			hsa05230
	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[38]
Response Summary	Knockdown of KIAA1429 significantly decreased the m6A levels of Protein BTG2 (BTG2) mRNA, leading to enhanced YTHDF2-dependent BTG2 mRNA stability and promoted the expression of BTG2; thus, participating in the tumorigenesis of LUAD.
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	HBE (Human bronchial epithelial cell line)
In-vivo Model	For the in vivo cell proliferation assay, A549 and SPCA1 cells were stably transfected with sh-Ctrl and sh-KIAA1429 using lentivirus (GeneChem, Shanghai, China). The cells were subcutaneously injected into either side of the posterior flanks of the mouse. The tumor volume was measured every few days (length×width2×0.5).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[29]
Response Summary	YTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the Protein FAM83D (FAM83D)-TGFbeta1-pSMAD2/3 pathway, which will play an important role in lung cancer metastasis.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[39]
Response Summary	FTO upregulated the expression of E2F1 by inhibiting the m6A modification of E2F1. The FTO/E2F1/Protein kinase C-binding protein NELL2 (NELL2) axis modulated NSCLC cell viability, migration, and invasion in vitro as well as affected NSCLC tumor growth and metastasis in vivo.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell viability
	Cell migration
	Cell invasion
In-vitro Model	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H23	Lung adenocarcinoma	Homo sapiens	CVCL_1547
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	The nude mice were maintained under pathogen-free conditions and kept under timed lighting conditions mandated by the committee with food and water provided ad libitum. For xenograft experiments, nude mice were injected subcutaneously with 5 × 106 cells resuspended in 0.1 mL PBS. When a tumor was palpable, it was measured every 3 days.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[26]
Response Summary	miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor KLF4. miR-1915-3p function as a tumor suppressor by targeting Protein SET (SET) and has an anti-metastatic therapeutic potential for lung cancer treatment.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	TNF signaling pathway			hsa04668
Cell Process	Cell migration
	Cell invasion
	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[26]
Response Summary	miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor KLF4. miR-1915-3p function as a tumor suppressor by targeting Protein SET (SET) and has an anti-metastatic therapeutic potential for lung cancer treatment.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	TNF signaling pathway			hsa04668
Cell Process	Cell migration
	Cell invasion
	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[40]
Response Summary	METTL3 contributes to the progression and chemoresistance of NSCLC by promoting RAC-alpha serine/threonine-protein kinase (AKT1) protein expression through regulating AKT1 mRNA m6A levels, and provides an efficient therapeutic intervention target for overcoming chemoresistance in NSCLC.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[37]
Response Summary	METTL3-mediated m6 A methylation promotes lung cancer progression via activating PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathway.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	5 × 106 A549 cells overexpressing METTL3 (Lv-METTL3) or control (Lv-Ctrl) were suspended in 100?uL phosphate-buffered saline (PBS), and were subcutaneously injected into mouse lower right flank. Drug treatment started in the Lv-METTL3 group when the tumour volume reached around 100 mm3. Mice were randomly divided into three groups to receive vehicle, GSK2536771 (30 mg/kg) or rapamycin (1 mg/kg). Drugs were administrated daily through intraperitoneal injection for 18 days. Treatment conditions were chosen as previously reported.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	In lung squamous cell carcinoma, seven m6A-related autophagy genes were screened to construct a prognostic model: CASP4, CDKN1A, Rho GTPase-activating protein 7 (DLC1), ITGB1, PINK1, TP63, and EIF4EBP1.
Responsed Disease	Lung squamous cell carcinoma [ICD-11: 2C25.2]
Pathway Response	Autophagy			hsa04140
Cell Process	Cell proliferation and metastasis
	Cell autophagy

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[41]
Response Summary	ABALON acted as a competing endogenous RNA by sponging miR-139-3p and indirectly regulated the expression of RNA-binding protein NOB1 (NOB1) in the occurrence of lung cancer.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Pathway Response	T cell receptor signaling pathway			hsa04660
	Ribosome biogenesis in eukaryotes			hsa03008
Cell Process	Immune

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[42]
Response Summary	HNRNPA2B1 inhibits Secreted frizzled-related protein 2 (SFRP2) and activates Wnt-Beta/catenin via m6A-mediated maturing of miR-106b-5p to aggravate stemness and LUAD progression.
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	A549 cells were transfected with lentivirus-packaged sh-HNRNPA2B1 (lv-sh-HNRNPA2B1) or control (lv-shCtrl). Then, each mouse was injected subcutaneously with A549 cells of indicated transfection group to generate xenografts. The tumor volume ((width2 × length)/2) was evaluated 4 days a time until 28 days.

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and Sequestosome-1 (SQSTM1). beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Chloroquine		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and Sequestosome-1 (SQSTM1). beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and Sequestosome-1 (SQSTM1). beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Beta-Elemen		Phase 3	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[43]
Response Summary	m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/Serine/threonine-protein kinase LATS2 (LATS2)-mediated YAP activity in non-small cell lung cancer.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Cell Process	Cell proliferation
	Cell invasion
	Cell migration
	Cell EMT
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	For the experiments, mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into indicated groups (five mice per group). To assess the in vivo effects of cycloleucine, the xenografted tumors had reached approximately 5 mm in diameter from mice and then these xenografted mice were feed with Vehicle or cycloleucine (25 mg/kg twice weekly) and tumor volume were measured every 3 day. Tumor volume was estimated as 0.5 × a2 × b (where a and b represent a tumors short and long diameter, respectively). Mice were euthanized after 7 weeks and the tumors were measured a final time.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[37]
Response Summary	METTL3-mediated m6 A methylation promotes lung cancer progression via activating PI3K/AKT/Serine/threonine-protein kinase mTOR (MTOR) pathway.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	5 × 106 A549 cells overexpressing METTL3 (Lv-METTL3) or control (Lv-Ctrl) were suspended in 100?uL phosphate-buffered saline (PBS), and were subcutaneously injected into mouse lower right flank. Drug treatment started in the Lv-METTL3 group when the tumour volume reached around 100 mm3. Mice were randomly divided into three groups to receive vehicle, GSK2536771 (30 mg/kg) or rapamycin (1 mg/kg). Drugs were administrated daily through intraperitoneal injection for 18 days. Treatment conditions were chosen as previously reported.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	In lung squamous cell carcinoma, seven m6A-related autophagy genes were screened to construct a prognostic model: CASP4, CDKN1A, DLC1, ITGB1, Serine/threonine-protein kinase PINK1, mitochondrial (PINK1), TP63, and EIF4EBP1.
Responsed Disease	Lung squamous cell carcinoma [ICD-11: 2C25.2]
Pathway Response	Autophagy			hsa04140
Cell Process	Cell proliferation and metastasis
	Cell autophagy

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[44]
Response Summary	ALKBH5 gain- or loss-of function could effectively reverse Serine/threonine-protein kinase STK11 (STK11/LKB1) regulated cell proliferation, colony formation, and migration of KRAS-mutated lung cancer cells.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	MRC-9	Normal	Homo sapiens	CVCL_2629
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	H1795 (Lung cancer H1795 cell lines were purchased from ATCC, USA)
	NCI-H1792	Lung adenocarcinoma	Homo sapiens	CVCL_1495
	NCI-H1703	Lung squamous cell carcinoma	Homo sapiens	CVCL_1490
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[30]
Response Summary	ALKBH5 weakens YTHDF1/3-mediated TGF-beta receptor type-2 (TGF-Beta-R2) and SMAD3 mRNA stabilization, and abolishes YTHDF2-mediated SMAD6 mRNA degradation, supporting the notion that ALKBH5 inhibits TGF-Beta-induced EMT and invasion of NSCLC cells via YTHD1/2/3-mediated mechanism.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Down regulation
Pathway Response	TGF-beta signaling pathway			hsa04350
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	The mice were divided into control group and ALKBH5-overexpressing group (9 mice per group). ALKBH5-overexpressing and control A549 cells (3 × 106 cells/mouse) in 200 uL PBS were intravenously (i.v.) injected into the lateral tail vein of mice. At every 5th day post-inoculation, TGF-Beta-1 (4 ug/kg body weight) was intraperitoneally (i.p.) injected to promote tumor cell metastasis. Eight weeks later, the mice were euthanized, and then their lungs and livers were taken out and fixed in Bouin's solution (Sigma Aldrich, HT101128) or 4% Paraformaldehyde (Beyotime, p0099, Shanghai, China) for macroscopically metastatic nodule analysis.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[45]
Response Summary	In lung cancer, IGF2BP2 modified m6A to increase the expression of Thymidine kinase, cytosolic (TK1), thus promoting angiogenesis.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	NHBE (Normal bronchial epithelial cells)
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	Suspension of H1299 cells (5.0 × 105) was subcutaneously injected into the right flanks of the mice.

In total 4 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[33]
Response Summary	This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher programmed death-ligand 1 (PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, Transcription factor E2F1 (E2F1) targets were significantly enriched.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Pathway Response	p53 signaling pathway			hsa04115
	Central carbon metabolism in cancer			hsa05230
	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[33]
Response Summary	This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher programmed death-ligand 1 (PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, Transcription factor E2F1 (E2F1) targets were significantly enriched.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Pathway Response	p53 signaling pathway			hsa04115
	Central carbon metabolism in cancer			hsa05230
	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[33]
Response Summary	This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher programmed death-ligand 1 (PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, Transcription factor E2F1 (E2F1) targets were significantly enriched.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Pathway Response	p53 signaling pathway			hsa04115
	Central carbon metabolism in cancer			hsa05230
	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene				[39]
Response Summary	FTO upregulated the expression of Transcription factor E2F1 (E2F1) by inhibiting the m6A modification of E2F1. The FTO/E2F1/NELL2 axis modulated NSCLC cell viability, migration, and invasion in vitro as well as affected NSCLC tumor growth and metastasis in vivo.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell viability
	Cell migration
	Cell invasion
In-vitro Model	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H23	Lung adenocarcinoma	Homo sapiens	CVCL_1547
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	The nude mice were maintained under pathogen-free conditions and kept under timed lighting conditions mandated by the committee with food and water provided ad libitum. For xenograft experiments, nude mice were injected subcutaneously with 5 × 106 cells resuspended in 0.1 mL PBS. When a tumor was palpable, it was measured every 3 days.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including Transcription factor E2F3 (E2F3), WTAP, CCND1, CDK4, EGR2, YBX1, and TLX, which were associated with lung cancers.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Cell Process	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	HBE (Human bronchial epithelial cell line)
	LTEP-a2	Endocervical adenocarcinoma	Homo sapiens	CVCL_6929
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including Transcription factor E2F3 (E2F3), WTAP, CCND1, CDK4, EGR2, YBX1, and TLX, which were associated with lung cancers.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Cell Process	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	HBE (Human bronchial epithelial cell line)
	LTEP-a2	Endocervical adenocarcinoma	Homo sapiens	CVCL_6929
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[46]
Response Summary	m6A methyltransferase METTL3 is indispensable for TGF-beta-induced EMT of lung cancer cells through the regulation of Transcription factor JunB (JUNB).
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Cytokine-cytokine receptor interaction			hsa04060
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	LC-2/ad	Lung adenocarcinoma	Homo sapiens	CVCL_1373

In total 5 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[47]
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-Transcriptional coactivator YAP1 (YAP1) axis to induce Non-small cell lung cancer drug resistance and metastasis.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[47]
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-Transcriptional coactivator YAP1 (YAP1) axis to induce Non-small cell lung cancer drug resistance and metastasis.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 3 (YTHDF3)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[47]
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-Transcriptional coactivator YAP1 (YAP1) axis to induce Non-small cell lung cancer drug resistance and metastasis.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene				[43]
Response Summary	m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated Transcriptional coactivator YAP1 (YAP1) expression and inhibiting miR-107/LATS2-mediated YAP activity in non-small cell lung cancer.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Cell Process	Cell proliferation
	Cell invasion
	Cell migration
	Cell EMT
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	For the experiments, mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into indicated groups (five mice per group). To assess the in vivo effects of cycloleucine, the xenografted tumors had reached approximately 5 mm in diameter from mice and then these xenografted mice were feed with Vehicle or cycloleucine (25 mg/kg twice weekly) and tumor volume were measured every 3 day. Tumor volume was estimated as 0.5 × a2 × b (where a and b represent a tumors short and long diameter, respectively). Mice were euthanized after 7 weeks and the tumors were measured a final time.
Experiment 5 Reporting the m6A-centered Disease Response by This Target Gene				[43]
Response Summary	YTHDF1 promoted Transcriptional coactivator YAP1 (YAP1) mRNA translation by interacting with eIF3a in NSCLC.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Eukaryotic initiation factor 3 (EIF3A)		READER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	3 to 5-week old female BALB/c athymic (NU/NU) nude mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into indicated groups (five mice per group). To assess the in vivo effects of cycloleucine, the xenografted tumors had reached approximately 5 mm in diameter from mice and then these xenografted mice were feed with Vehicle or cycloleucine (25 mg/kg twice weekly) and tumor volume were measured every 3 day.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[29]
Response Summary	YTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the FAM83D-Transforming growth factor beta-1 proprotein (TGFB1)-pSMAD2/3 pathway, which will play an important role in lung cancer metastasis.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	In lung squamous cell carcinoma, seven m6A-related autophagy genes were screened to construct a prognostic model: CASP4, CDKN1A, DLC1, ITGB1, PINK1, Tumor protein 63 (TP63), and EIF4EBP1.
Responsed Disease	Lung squamous cell carcinoma [ICD-11: 2C25.2]
Pathway Response	Autophagy			hsa04140
Cell Process	Cell proliferation and metastasis
	Cell autophagy

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[48]
Response Summary	The m6A demethylase FTO promotes the growth of Non-small cell lung cancer cells by increasing the expression of USP7.Genetic knockdown or pharmacological inhibition (P5091 or P22027) of Ubiquitin carboxyl-terminal hydrolase 7 (USP7) reduced the proliferation rate of lung cancer cells and decreased the capacity of colony formation of lung cancer cells in vitro, whereas lung cancer cells growth inhibition by FTO knockdown is restored by overexertion of USP7.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	P22077		Investigative	Drug Info
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Cell Process	Ubiquitination degradation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H522	Lung adenocarcinoma	Homo sapiens	CVCL_1567
	HSAEC (Human small airway epithelial cells)
	RERF-LC-A1	Lung squamous cell carcinoma	Homo sapiens	CVCL_4402
	NCI-H1882	Lung small cell carcinoma	Homo sapiens	CVCL_1504
	NCl-H466 (Human lung cancer cell line)
In-vivo Model	Equal numbers of A549 cells expressing either control or shFTO were injected subcutaneously, within 30 min of harvesting, over the right and left flanks in male nu/nu mice between 4 and 6 weeks of age.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[48]
Response Summary	The m6A demethylase FTO promotes the growth of Non-small cell lung cancer cells by increasing the expression of USP7.Genetic knockdown or pharmacological inhibition (P5091 or P22027) of Ubiquitin carboxyl-terminal hydrolase 7 (USP7) reduced the proliferation rate of lung cancer cells and decreased the capacity of colony formation of lung cancer cells in vitro, whereas lung cancer cells growth inhibition by FTO knockdown is restored by overexertion of USP7.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	P5091		Investigative	Drug Info
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Cell Process	Ubiquitination degradation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H522	Lung adenocarcinoma	Homo sapiens	CVCL_1567
	HSAEC (Human small airway epithelial cells)
	RERF-LC-A1	Lung squamous cell carcinoma	Homo sapiens	CVCL_4402
	NCI-H1882	Lung small cell carcinoma	Homo sapiens	CVCL_1504
	NCl-H466 (Human lung cancer cell line)
In-vivo Model	Equal numbers of A549 cells expressing either control or shFTO were injected subcutaneously, within 30 min of harvesting, over the right and left flanks in male nu/nu mice between 4 and 6 weeks of age.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[49]
Response Summary	Smoking-related downregulation of YTHDC2 was associated with enhanced proliferation and migration in lung cancer cells, YTHDC2 functions as a tumor suppressor through the Ubiquitin carboxyl-terminal hydrolase CYLD (CYLD)/NF-Kappa-B signaling pathway, which is mediated by m6A modification.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	YTH domain-containing protein 2 (YTHDC2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
In-vivo Model	Approximately 5×106 normal H1299 cells or stable YTHDC2-overexpressing H1299 cells were implanted subcutaneously into the right flank of the animals (n=8 mice per group). Animals were euthanized by cervical dislocation ~30 days after implantation, and tumors were collected and photographed.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[50]
Response Summary	Deregulated Ubiquitin-conjugating enzyme E2 C (UBE2C)-autophagy repression axis drives NSCLC progression which renders varieties of potential molecular targets in cancer therapy of NSCLC. UBE2C is repressed post-transcriptionally via tumor suppressor miR-381 and epitranscriptionally stabilized with maintenance of lower m6A level within its mature RNAs due to the upregulation of m6A demethylase ALKBH5 in NSCLC.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell invasion
	Ubiquitination degradation
	Cell autophagy
In-vitro Model	PLA-801D	Lung giant cell carcinoma	Homo sapiens	CVCL_7110
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	HBEC (Human lung cancer cell)
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Chloroquine		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Beta-Elemen		Phase 3	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[51]
Response Summary	Up-regulation of Vang-like protein 1 (VANGL1) by IGF2BPs and miR-29b-3p attenuates the detrimental effect of irradiation on lung adenocarcinoma. Increased m6A level of VANGL1 and reduced miR-29b-3p took the responsibility of VANGL1 overexpression upon irradiation.
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	DNA repair
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
In-vivo Model	Two hundred milliliters of A549 cells (1 × 106) were injected into the left flank of the back of each mouse.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including E2F3, WTAP, CCND1, CDK4, EGR2, Y-box-binding protein 1 (YBX1), and TLX, which were associated with lung cancers.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Cell Process	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	HBE (Human bronchial epithelial cell line)
	LTEP-a2	Endocervical adenocarcinoma	Homo sapiens	CVCL_6929
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including E2F3, WTAP, CCND1, CDK4, EGR2, Y-box-binding protein 1 (YBX1), and TLX, which were associated with lung cancers.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Cell Process	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	HBE (Human bronchial epithelial cell line)
	LTEP-a2	Endocervical adenocarcinoma	Homo sapiens	CVCL_6929
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[52]
Response Summary	METTL3-mediated m6A modification of Zinc finger and BTB domain-containing protein 4 (ZBTB4) via EZH2 is involved in the CS-induced EMT and in lung cancer.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	HBE (Human bronchial epithelial cell line)
In-vivo Model	Male BALB/c mice were grouped into control, CS, CS+AAV-ShMETTL3, and CS+AAV-NC shRNA groups, n = 6 animals per group. Mice in the AAV-ShMETTL3 and AAV-NC shRNA (GeneChem, China) groups were dosed by intranasal instillation after CS exposure for 4 weeks.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[41]
Response Summary	Apoptotic BCL2L1-antisense long non-coding RNA (ABALON) acted as a competing endogenous RNA by sponging miR-139-3p and indirectly regulated the expression of NOB1 in the occurrence of lung cancer.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Pathway Response	T cell receptor signaling pathway			hsa04660
	Ribosome biogenesis in eukaryotes			hsa03008
Cell Process	Immune

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[53]
Response Summary	FEZF1 antisense RNA 1 (FEZF1-AS1) was upregulated and acted as an oncogene in non-small cell lung cancer by regulating the ITGA11/miR-516b-5p axis, suggesting that FEZF1-AS1 is a potential prognostic biomarker and therapeutic target for NSCLC.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell proliferation and migration
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1703	Lung squamous cell carcinoma	Homo sapiens	CVCL_1490
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	NSCLC H358 (Human non-small cell lung cancer cells)
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[54]
Response Summary	HLA complex group 11 (HCG11) mediated by METTL14 inhibited the growth of lung adenocarcinoma via IGF2BP2/LATS1. The m6A modification of HCG11 promoted its nuclear exportation and binding by Insulin Like Growth Factor 2 MRNA Binding Protein 2 (IGF2BP2), resulting in increased stability.
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stabilization
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	HBE (Human bronchial epithelial cell line)
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H522	Lung adenocarcinoma	Homo sapiens	CVCL_1567
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	LUAD cells stably HCG11 and/or LATS1 overexpressed or silenced were subcutaneously injected into the flank of the BALB/c nude mice (male, 4 weeks old).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[54]
Response Summary	HLA complex group 11 (HCG11) mediated by METTL14 inhibited the growth of lung adenocarcinoma via IGF2BP2/LATS1. The m6A modification of HCG11 promoted its nuclear exportation and binding by Insulin Like Growth Factor 2 MRNA Binding Protein 2 (IGF2BP2), resulting in increased stability.
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stabilization
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	HBE (Human bronchial epithelial cell line)
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H522	Lung adenocarcinoma	Homo sapiens	CVCL_1567
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	LUAD cells stably HCG11 and/or LATS1 overexpressed or silenced were subcutaneously injected into the flank of the BALB/c nude mice (male, 4 weeks old).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[55]
Response Summary	LINC00035 (ABHD11-AS1) was upregulated in NSCLC tissue specimens and cells and the ectopic overexpression was closely correlated with unfavorable prognosis of NSCLC patients.METTL3 installed the m6 A modification and enhanced ABHD11-AS1 transcript stability to increase its expression.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Central carbon metabolism in cancer			hsa05230
In-vitro Model	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	H1299 cells were transfected with sh-ABHD11-AS1 and harvested from six-well plates, then resuspended at a density 1 × 107 cells/ml. Mice were subsequently injected with 100 uL suspension at the right flank. After injection, tumor weight and length were examined every 3 days.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[56]
Response Summary	In lung adenocarcinoma, The miR-146a/Notch signaling was sustained highly activated in a m6A dependent manner, and the m6A regulator of YTHDF2 suppressed LINC00902 (TUSC7), both of which contributed to the resistant features. Functionally, the sponge type of TUSC7 regulation of miR-146a inhibited Notch signaling functions, and affected the cancer progression and stem cells' renewal in Erlotinib resistant PC9 cells (PC9ER) and Erlotinib resistant HCC827 cells (HCC827ER) cells.
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Responsed Drug	Erlotinib		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Notch signaling pathway			hsa04330), EGFR tyrosine kinase inhibitor resistance
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
In-vivo Model	Control vector, TUSC7 knockout, FLI-06 treated H1975 cells (1*107) cells were suspended in 100 uL of serum-free DMEM medium (Hyclone, USA), mixed with matrix gel (Corning, USA), and then were injected subcutaneously. The changes in the tumor size were recorded every 3 or 5 days.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[57]
Response Summary	m6A transferase METTL3-induced Long intergenic non-protein coding RNA 1833 (LINC01833) m6A methylation promotes NSCLC progression through modulating HNRNPA2B1 expression.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	For the tumorigenicity studies, 3 × 106 HCC827 cells stably expressing sh-LINC01833 or sh-NC were injected subcutaneously into the ventral side of male BALB/c nude mice in the according groups with five mice in each group. Five mice were sampled each time. Tumor size and weight were examined at 28 days after injection.

In total 4 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[47]
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 3 (YTHDF3)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[47]
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[47]
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene				[58]
Response Summary	IGF2BP2 promotes Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) stability in an m6A-dependent mechanism, thus promoting its downstream target autophagy-related (ATG)12 expression and NSCLC proliferation.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Lysosome			hsa04142
Cell Process	Cell autophagy
In-vitro Model	NCI-H157	Lung squamous cell carcinoma	Homo sapiens	CVCL_0463
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1703	Lung squamous cell carcinoma	Homo sapiens	CVCL_1490
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	Mice (male and 6 weeks old) were subcutaneously injected with NSCLC cells (1.0*106 cells/200 uL). The mice were terminated after 4 weeks of induction, and the tumor volume and tumor weight were measured.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[59]
Response Summary	m6A RNA methylation-mediated RMRP stability renders proliferation and progression of non-small cell lung cancer through regulating TGFBR1/SMAD2/SMAD3 pathway. RMRP promoted the cancer stem cells properties and epithelial mesenchymal transition, which promote the resistance to radiation therapy and cisplatin.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Pathway Response	Signaling pathways regulating pluripotency of stem cells			hsa04550
	EGFR tyrosine kinase inhibitor resistance			hsa01521
Cell Process	Epithelial mesenchymal transition
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[60]
Response Summary	ALKBH5 knockdown, was able to inhibit malignant behavior of lung adenocarcinoma by regulating RMRP expression via demethylation. RMRP and ALKBH5 therefore represent promising therapeutic targets for lung adenocarcinoma.
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	XWLC-05	Lung adenocarcinoma	Homo sapiens	CVCL_IQ71
In-vivo Model	The mice were maintained in cages under standard environmental conditions (temperature 25 ± 2 ℃, humidity 55 ± 5% and 12-h light/12-h dark cycle) and given free access to food and tap water. All mice were randomly divided into three groups with 6 in each group. To establish xenograft model, A549 cells (1 × 107) transfected with si-control (si-NC), si-ALKBH5 or si-ALKBH5 + RMRP were injected subcutaneously into a single side of the armpit of each mouse.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[61]
Response Summary	METTL3/Small nucleolar RNA host gene 1 (SNHG1)/miR-140-3p/UBE2C axis plays a crucial role in cancer progression and the immune response in non-small cell lung cancer.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[62]
Response Summary	The reduction in cell proliferation induced by SVIL antisense RNA 1 (SVIL-AS1) overexpression could be rescued by E2F1 overexpression or METTL3 knockdown. In conclusion, METTL3-induced SVIL-AS1 in LUAD, which connects m6A and lncRNA in lung cancer carcinogenesis.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	A549 cells (1 × 106 cells) were intraperitoneally injected into the abdomen of nude mice. Tumor length and width were measured and recorded every 4 days after inoculation. Tumor volume was calculated as 1/2 × length × width2. The tumor weight was weighed and recorded 20 days after inoculation.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[43]
Response Summary	m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting microRNA 107 (MIR107)/LATS2-mediated YAP activity in non-small cell lung cancer.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Cell Process	Cell proliferation
	Cell invasion
	Cell migration
	Cell EMT
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	For the experiments, mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into indicated groups (five mice per group). To assess the in vivo effects of cycloleucine, the xenografted tumors had reached approximately 5 mm in diameter from mice and then these xenografted mice were feed with Vehicle or cycloleucine (25 mg/kg twice weekly) and tumor volume were measured every 3 day. Tumor volume was estimated as 0.5 × a2 × b (where a and b represent a tumors short and long diameter, respectively). Mice were euthanized after 7 weeks and the tumors were measured a final time.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	METTL3 regulates the m6A modification to promote the maturation of microRNA 1246 (MIR1246), which targets PEG3 to participate in occurrence and development of non-small cell lung cancer.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	The 40 nude mice of each large group were classified into 8 small groups (n = 5) and subcutaneously injected with transfected cell suspension in the back (5 × 106 cells/mL/mouse). The length and width of tumors were recorded every 4 days, and the tumor volume = (length × width2)/2. The tumor growth curve was thereby graphed. On the 28th day of injection, mice were euthanized by neck dislocation, and the xenografts were harvested, photographed, and weighed

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[63]
Response Summary	the participation of Metformin decreased the bindings of DNMT3a/b to the METTL3 promoter with the help of the readers of NKAP and HNRNPA2B1.the mediation of m6A formation on pri-Let-7b processing increased the mature microRNA let-7b (MIRLET7B), whose key role is to suppress the Notch signaling and to re-captivate the Osimertinib treatment.The findings open up future drug development, targeting this pathway for lung cancer patients.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Responsed Drug	Metformin		Approved	Drug Info
Target Regulator	NF-kappa-B-activating protein (NKAP)		READER	Regulator Info
Pathway Response	Notch signaling pathway			hsa04330
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	H1975OR (Osimertinib resistant H1975 cells)
	HCC827OR (Osimertinib resistant HCC827 cells)
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[63]
Response Summary	the participation of Metformin decreased the bindings of DNMT3a/b to the METTL3 promoter with the help of the readers of NKAP and HNRNPA2B1.the mediation of m6A formation on pri-Let-7b processing increased the mature microRNA let-7b (MIRLET7B), whose key role is to suppress the Notch signaling and to re-captivate the Osimertinib treatment.The findings open up future drug development, targeting this pathway for lung cancer patients.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Responsed Drug	Osimertinib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Pathway Response	Notch signaling pathway			hsa04330
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	H1975OR (Osimertinib resistant H1975 cells)
	HCC827OR (Osimertinib resistant HCC827 cells)

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[41]
Response Summary	ABALON acted as a competing endogenous RNA by sponging hsa-miR-139-3p and indirectly regulated the expression of NOB1 in the occurrence of lung cancer.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Pathway Response	T cell receptor signaling pathway			hsa04660
	Ribosome biogenesis in eukaryotes			hsa03008
Cell Process	Immune

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[61]
Response Summary	METTL3/SNHG1/hsa-miR-140-3p/UBE2C axis plays a crucial role in cancer progression and the immune response in non-small cell lung cancer.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[64]
Response Summary	m6A methyltransferase Mettl3 can increase the splicing of precursor hsa-miR-143-3p to facilitate its biogenesis. The miR-143-3p/VASH1 axis in BM of lung cancers and suggests their critical roles in lung cancer pathogenesis.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	RNA splicing
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
In-vivo Model	For subcutaneous transplanted model, control and miR-143-3p stable A549 cells (5 × 106 per mouse, n = 5 for each group) were diluted in 200 uL PBS + 200 uL Matrigel (BD Biosciences) and subcutaneously injected into immunodeficient mice to investigate tumor growth.

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[47]
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-hsa-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[47]
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-hsa-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 3 (YTHDF3)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[47]
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-hsa-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[26]
Response Summary	hsa-miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor KLF4. miR-1915-3p function as a tumor suppressor by targeting SET and has an anti-metastatic therapeutic potential for lung cancer treatment.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	TNF signaling pathway			hsa04668
Cell Process	Cell migration
	Cell invasion
	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[26]
Response Summary	hsa-miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor KLF4. miR-1915-3p function as a tumor suppressor by targeting SET and has an anti-metastatic therapeutic potential for lung cancer treatment.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	TNF signaling pathway			hsa04668
Cell Process	Cell migration
	Cell invasion
	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[65]
Response Summary	In non-small cell lung cancer, m6A marks in mature hsa-miR-21-5p could directly affect its silencing potency towards target genes, which finally impaired its promotion to proliferation and motility. Depletion of the demethylase ALKBH5 altered the m6A abundance of miR-21-5p, thereby changing the expression levels of its target gene.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	HEK293-A	Normal	Homo sapiens	CVCL_6910

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[66]
Response Summary	METTL14 was remarkably downregulated in LC tissues and cell lines. METTL14 mediated the maturation of hsa-miR-30c-1-3p.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	miRNA maturation
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	The cells (1 × 106) were re-suspended in normal saline and mixed with 25% Matrigel matrix (50 uL) at a 1:1 ratio and subcutaneously injected into the right groin of the mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[67]
Response Summary	GPER promotes non-small-cell lung cancer cell growth by regulating YAP1-TEAD/QKI/circNOTCH1/m6A methylated NOTCH1 signalling. Further exploration of the mechanism demonstrated that GPER could up-regulate hsa_circ_0089552 (circNOTCH1), which could compete with NOTCH1 mRNA for METTL14 binding.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Notch signaling pathway			hsa04330
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
In-vivo Model	Thirty-two 6 week-old female nude mice divided into four groups (n = 8 per group) for injections of H1299 cells transfected with (a) pLKO.1 + pWPI, (b) shcircNOTCH1 + pWPI, (c) pLKO.1 + oeGPER and (d) shcircNOTCH1 + oeGPER.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[68]
Response Summary	Increased YTHDF2-mediated endoribonucleolytic cleavage of m6A-modified Circ_ASK1 accounts for its downregulation in gefitinib-resistant cells. Either METTL3 silencing or YTHDF2 silencing suppressed the decay of circASK1 in HCC827-GR cells. This study provides a novel therapeutic target to overcome gefitinib resistance in LUAD patients.
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Cell Process	Cell apoptosis
In-vitro Model	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
	SK-LU-1	Lung adenocarcinoma	Homo sapiens	CVCL_0629
	NCI-H1993	Lung adenocarcinoma	Homo sapiens	CVCL_1512
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	Established a xenograft model in BALB/c nude mice by inoculating HCC827-GR cells transfected with the constructs for circASK1 silencing, ASK1-272a.a overexpression and ASK1-272a.a overexpression/circASK1 knockdown
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[68]
Response Summary	Increased YTHDF2-mediated endoribonucleolytic cleavage of m6A-modified Circ_ASK1 accounts for its downregulation in gefitinib-resistant cells. Either METTL3 silencing or YTHDF2 silencing suppressed the decay of circASK1 in HCC827-GR cells. This study provides a novel therapeutic target to overcome gefitinib resistance in LUAD patients.
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
	SK-LU-1	Lung adenocarcinoma	Homo sapiens	CVCL_0629
	NCI-H1993	Lung adenocarcinoma	Homo sapiens	CVCL_1512
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	Established a xenograft model in BALB/c nude mice by inoculating HCC827-GR cells transfected with the constructs for circASK1 silencing, ASK1-272a.a overexpression and ASK1-272a.a overexpression/circASK1 knockdown

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[69]
Response Summary	In non-small-cell lung carcinoma, METTL3 mediates the N6-methyladenosine (m6A) modification of Circ_IGF2BP3 and promotes its circularization in a manner dependent on the m6A reader protein YTHDC1.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	SW900	Lung squamous cell carcinoma	Homo sapiens	CVCL_1731
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1703	Lung squamous cell carcinoma	Homo sapiens	CVCL_1490
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	A total of 106 LLC cells transfected with the following constructs were injected subcutaneously into C57BL/6 mice.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[69]
Response Summary	In non-small-cell lung carcinoma, METTL3 mediates the N6-methyladenosine (m6A) modification of Circ_IGF2BP3 and promotes its circularization in a manner dependent on the m6A reader protein YTHDC1.
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator	YTH domain-containing protein 1 (YTHDC1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	SW900	Lung squamous cell carcinoma	Homo sapiens	CVCL_1731
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1703	Lung squamous cell carcinoma	Homo sapiens	CVCL_1490
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	A total of 106 LLC cells transfected with the following constructs were injected subcutaneously into C57BL/6 mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[19]
Response Summary	LCAT3 upregulation is attributable to N6-methyladenosine (m6A) modification mediated by methyltransferase like 3 (METTL3), leading to LCAT3 stabilization. LCAT3 as a novel oncogenic lncRNA in the lung, and validated the LCAT3-FUBP1-MYC axis as a potential therapeutic target for lung adenocarcinomas.
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0608
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HOP-62	Lung adenocarcinoma	Homo sapiens	CVCL_1285
In-vivo Model	For the in vivo tumorigenicity assay, female BALB/c nude mice (ages 4-5 weeks) were randomly divided into two groups (n = 6/group). Calu1 cells (4 × 106) that had been stably transfected with sh-LCAT3 or scramble were implanted subcutaneously into the nude mice. Tumor growth was measured after one week, and tumor volumes were calculated with the following formula: Volume (cm3) = (length × width2)/2. After four weeks, the mice were euthanized, and the tumors were collected and weighed. For the in vivo tumor invasion assay, 1.2 × 106 scramble or shLCAT3 cells were injected intravenously into the tail vein of nude mice (n = 6/group). 1.5 mg luciferin (Gold Biotech, St Louis, MO, USA) was administered once a week for 4 weeks, to monitor metastases using an IVIS@ Lumina II system (Caliper Life Sciences, Hopkinton, MA, USA).