Name	Cervical cancer
ICD	ICD-11: 2C77

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	METTL3 interacts with IGF2BP3 to promote the mRNA stability of Apoptotic chromatin condensation inducer in the nucleus (ACIN1), the overexpression of which induces the aggressiveness of CC cells.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	End1/E6E7	Normal	Homo sapiens	CVCL_3684
In-vivo Model	2 × 106 stably transfected HeLa cells were subcutaneously inoculated into the left flank of mice.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	METTL3 interacts with IGF2BP3 to promote the mRNA stability of Apoptotic chromatin condensation inducer in the nucleus (ACIN1), the overexpression of which induces the aggressiveness of CC cells.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	End1/E6E7	Normal	Homo sapiens	CVCL_3684
In-vivo Model	2 × 106 stably transfected HeLa cells were subcutaneously inoculated into the left flank of mice.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	DARS-AS1 was validated to facilitate DARS translation via recruiting METTL3 and METTL14, which bound with DARS mRNA Aspartate--tRNA ligase, cytoplasmic (DARS) mRNA 5' untranslated region (5'UTR) and promoting its translation. The present study demonstrated that the 'HIF1-Alpha/DARS-AS1/DARS/ATG5/ATG3' pathway regulated the hypoxia-induced cytoprotective autophagy of cervical cancer(CC) and is a promising target of therapeutic strategies for patients afflicted with CC.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	End1/E6E7	Normal	Homo sapiens	CVCL_3684
	DoTc2 4510	Cervical carcinoma	Homo sapiens	CVCL_1181
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	DARS-AS1 was validated to facilitate DARS translation via recruiting METTL3 and METTL14, which bound with DARS mRNA Aspartate--tRNA ligase, cytoplasmic (DARS) mRNA 5' untranslated region (5'UTR) and promoting its translation. The present study demonstrated that the 'HIF1-Alpha/DARS-AS1/DARS/ATG5/ATG3' pathway regulated the hypoxia-induced cytoprotective autophagy of cervical cancer(CC) and is a promising target of therapeutic strategies for patients afflicted with CC.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	End1/E6E7	Normal	Homo sapiens	CVCL_3684
	DoTc2 4510	Cervical carcinoma	Homo sapiens	CVCL_1181
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	YTHDF2 interference could suppress the EMT of cervical cancer cells and enhance cisplatin chemosensitivity by regulating Axin-1 (AXIN1).
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Ect1/E6E7	Normal	Homo sapiens	CVCL_3679
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	The study revealed firm links between m6A modification patterns and cervical cancer prognosis, especially through ZC3H13-mediated m6A modification of Centromere protein K (CENPK) mRNA.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Zinc finger CCCH domain-containing protein 13 (ZC3H13)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
	p53 signaling pathway			hsa04115
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
In-vivo Model	BALB/c-nu mice were grouped as follows to detect tumor growth: HeLa-sh-NC [mice inoculated with scramble shRNA-infected control HeLa cells (n = 5)] and HeLa-sh-CENPK [mice inoculated with CENPK-targeted shRNA-infected HeLa cells (n = 5)]. The mice were subcutaneously inoculated with 5 × 106 cells/100 uL in the flank. The longest and the shortest diameters of the growing tumors were measured every 3 d with a caliper, and the tumor volume (V) was counted by the following equation: V = (the longest diameter × the shortest diameter2)/2. The mice were grouped as follows to evaluate the tumor-initiating frequency and were inoculated with a series of 5 × 105, 2 × 105, and 5 × 104 cells subcutaneously: HeLa-sh-NC (n = 6); and HeLa-sh-CENPK (n = 6). The mice bearing subcutaneous xenograft tumors were grouped as follows to evaluate tumor chemoresistance: HeLa-sh-NC (n = 10); HeLa-sh-CENPK (n = 10); HeLa-sh-NC + cisplatin [mice inoculated with scramble shRNA-infected control HeLa cells and 3 mg/kg of cisplatin once a week intraperitoneally (ip) for 6 weeks (n = 10)].

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	The oncogenic role of YTHDF1 in cervical cancer by regulating E3 SUMO-protein ligase RanBP2 (RANBP2) expression and YTHDF1 represents a potential target for cervical cancer therapy.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell growth
	Cell migration
	Cell invasion
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
In-vivo Model	Balb/c female nude mice at 4-6 weeks old were injected with 4 × 106 cells subcutaneously on the back.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[9]
Response Summary	In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an m6A-dependent manner under normal and stress conditions and therefore affect gene expression output. Four representative high confidence targets, including MYC, Fascin (FSCN1), TK1, and MARCKSL1, exhibit strong binding with IGF2BPs around their m6A motifs in control cells. Knocking down of each individual IGF2BPs in Hela (cervical cancer) and HepG2 (liver cancer) cells significantly repressed MYC expression.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Cell Process	RNA decay
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	METTL3 modulates miR-193b mature process in an m6A-dependent manner. Reintroduction of miR-193b profoundly inhibits tumorigenesis of cervical cancer cells both in vivo and in vitro through G1/S-specific cyclin-D1 (CCND1) targeting.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
In-vivo Model	Mice were divided into two groups (n = 4/group) randomly. 3×106 cells suspended in 200 uL PBS were administered via subcutaneous injection over the right flank region of nude mice. After the development of palpable tumors (average volume, 50 mm3), intratumoral injection of synthetic miR-193b, or negative control complexed with siPORT Amine transfection reagent (Ambion, USA) was given 6 times at a 4-day interval.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	METTL3 enhanced the Hexokinase-2 (HK2) stability through YTHDF1-mediated m6A modification, thereby promoting the Warburg effect of CC, which promotes a novel insight for the CC treatment.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010), Central carbon metabolism in cancer
Cell Process	Glycolysis
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	HT-3	Cervical carcinoma	Homo sapiens	CVCL_1293
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
In-vivo Model	Five-week-old male nude BALB/C mice were applied for this animal studies and fed with certified standard diet and tap water ad libitum in a light/dark cycle of 12 h on/12 h off.The assay was performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Stable transfection of METTL3 knockdown (sh-METTL3) or negative control (sh-blank) in SiHa cells (5 × 106 cells per 0.1 mL) were injected into the flank of mice.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	METTL3 enhanced the Hexokinase-2 (HK2) stability through YTHDF1-mediated m6A modification, thereby promoting the Warburg effect of CC, which promotes a novel insight for the CC treatment.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010), Central carbon metabolism in cancer
Cell Process	Glycolysis
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	HT-3	Cervical carcinoma	Homo sapiens	CVCL_1293
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
In-vivo Model	Five-week-old male nude BALB/C mice were applied for this animal studies and fed with certified standard diet and tap water ad libitum in a light/dark cycle of 12 h on/12 h off.The assay was performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Stable transfection of METTL3 knockdown (sh-METTL3) or negative control (sh-blank) in SiHa cells (5 × 106 cells per 0.1 mL) were injected into the flank of mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[9]
Response Summary	In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an m6A-dependent manner under normal and stress conditions and therefore affect gene expression output. Four representative high confidence targets, including MYC, FSCN1, TK1, and MARCKS-related protein (MARCKSL1), exhibit strong binding with IGF2BPs around their m6A motifs in control cells. Knocking down of each individual IGF2BPs in Hela (cervical cancer) and HepG2 (liver cancer) cells significantly repressed MYC expression.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Cell Process	RNA decay
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[9]
Response Summary	In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an m6A-dependent manner under normal and stress conditions and therefore affect gene expression output. Four representative high confidence targets, including Myc proto-oncogene protein (MYC), FSCN1, TK1, and MARCKSL1, exhibit strong binding with IGF2BPs around their m6A motifs in control cells. Knocking down of each individual IGF2BPs in Hela (cervical cancer) and HepG2 (liver cancer) cells significantly repressed MYC expression.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Cell Process	RNA decay
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[14]
Response Summary	FTO interacts with transcripts of E2F1 and Myc proto-oncogene protein (MYC), inhibition of FTO significantly impairs the translation efficiency of E2F1 and Myc.FTO plays important oncogenic role in regulating cervical cancer cells' proliferation.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation and migration
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[9]
Response Summary	In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an m6A-dependent manner under normal and stress conditions and therefore affect gene expression output. Four representative high confidence targets, including MYC, FSCN1, Thymidine kinase, cytosolic (TK1), and MARCKSL1, exhibit strong binding with IGF2BPs around their m6A motifs in control cells. Knocking down of each individual IGF2BPs in Hela (cervical cancer) and HepG2 (liver cancer) cells significantly repressed MYC expression.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Cell Process	RNA decay
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[14]
Response Summary	FTO interacts with transcripts of Transcription factor E2F1 (E2F1) and Myc, inhibition of FTO significantly impairs the translation efficiency of E2F1 and Myc.FTO plays important oncogenic role in regulating cervical cancer cells' proliferation.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation and migration
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[19]
Response Summary	METTL3/FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) accelerates cervical cancer progression via a m6A-dependent modality, which serves as a potential therapeutic target for cervical cancer.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell migration and proliferation
In-vitro Model	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	HaCaT	Normal	Homo sapiens	CVCL_0038
	HT-3	Cervical carcinoma	Homo sapiens	CVCL_1293
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
In-vivo Model	A total 5 × 106 stably transfected SiHa cells were subcutaneously injected into the flank of nude mice.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[20]
Response Summary	The GAS5-AS1 expression in cervical cancer tissues was markedly decreased when compared with that in the adjacent normal tissues. GAS5-AS1 interacted with the tumor suppressor Growth arrest specific 5 (GAS5), and increased its stability by interacting with RNA demethylase ALKBH5 and decreasing GAS5 N6-methyladenosine (m6A) modification. m6A-mediated GAS5 RNA degradation relied on the m6A reader protein YTHDF2-dependent pathway.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation and metastasis
In-vitro Model	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	Normal cervical epithelium cell line (HCvEpC) (Isolated from cervical tissue)
In-vivo Model	200 uL PBS containing 1×107 cells of stable cells were subcutaneously injected into male BALB/c athymic nude mice (6-week old, 18-20 g).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[20]
Response Summary	The GAS5-AS1 expression in cervical cancer tissues was markedly decreased when compared with that in the adjacent normal tissues. GAS5-AS1 interacted with the tumor suppressor Growth arrest specific 5 (GAS5), and increased its stability by interacting with RNA demethylase ALKBH5 and decreasing GAS5 N6-methyladenosine (m6A) modification. m6A-mediated GAS5 RNA degradation relied on the m6A reader protein YTHDF2-dependent pathway.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation and metastasis
In-vitro Model	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	Normal cervical epithelium cell line (HCvEpC) (Isolated from cervical tissue)
In-vivo Model	200 uL PBS containing 1×107 cells of stable cells were subcutaneously injected into male BALB/c athymic nude mice (6-week old, 18-20 g).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[21]
Response Summary	FTO-stabilized HOXC13 antisense RNA (HOXC13-AS) epigenetically up-regulated FZD6 and activated Wnt/beta-catenin signaling to drive cervical cancer proliferation, invasion, and EMT, suggesting HOXC13-AS as a potential target for cervical cancer treatment.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Cell proliferation
	Cell invasion
	Epithelial-mesenchymal transition
In-vitro Model	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
	C-4-I	Cervical squamous cell carcinoma	Homo sapiens	CVCL_2253
	Ect1/E6E7	Normal	Homo sapiens	CVCL_3679
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[22]
Response Summary	KCNMB2 antisense RNA 1 (KCNMB2-AS1) and IGF2BP3 formed a positive regulatory circuit that enlarged the tumorigenic effect of KCNMB2-AS1 in cervical cancer.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
In-vivo Model	A total of 1 × 107 control or KCNMB2-AS1-depleted SiHa cells were resuspended in 0.1 ml phosphate-buffered saline and inoculated into the armpit of 5-week-old male 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				[23]
Response Summary	ZNFX1 antisense RNA 1 (ZFAS1) sequestered miR-647, and this RNA-RNA interaction is regulated by METLL3-mediated m6A modification in cervical cancer.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
In-vivo Model	Nude mice were subjected to a subcutaneous injection of 5× 106 control and ZFAS1 silencing CaSki cells suspended in 0.2 mL DMEM medium.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	METTL3 modulates miR-193b mature process in an m6A-dependent manner. Reintroduction of hsa-miR-193b profoundly inhibits tumorigenesis of cervical cancer cells both in vivo and in vitro through CCND1 targeting.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
In-vivo Model	Mice were divided into two groups (n = 4/group) randomly. 3×106 cells suspended in 200 uL PBS were administered via subcutaneous injection over the right flank region of nude mice. After the development of palpable tumors (average volume, 50 mm3), intratumoral injection of synthetic miR-193b, or negative control complexed with siPORT Amine transfection reagent (Ambion, USA) was given 6 times at a 4-day interval.

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-modified hsa_circ_0000231 (circARHGAP12) interacts with IGF2BP2 to enhance FOXM1 mRNA stability, forming circARHGAP12/IGF2BP2/FOXM1 complex, thereby promoting the proliferation and migration of cervical cancer cells.
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Cellular senescence			hsa04218
In-vitro Model	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	HaCaT	Normal	Homo sapiens	CVCL_0038
	HT-3	Cervical carcinoma	Homo sapiens	CVCL_1293
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
In-vivo Model	CircARHGAP12-stable knockdown cervical cancer cells (100 uL PBS containing 5 × 106 cells) were subcutaneously injected into the lateral flank of BALB/c nude mice.

Ref 1	ClinicalTrials.gov (NCT04050709) QUILT 3.064: PD-L1 t-haNK In Subjects With Locally Advanced Or Metastatic Solid Cancers. U.S. National Institutes of Health.
Ref 2	Methyltransferase-like 3 induces the development of cervical cancer by enhancing insulin-like growth factor 2 mRNA-binding proteins 3-mediated apoptotic chromatin condensation inducer 1 mRNA stability. Bioengineered. 2022 Mar;13(3):7034-7048. doi: 10.1080/21655979.2022.2044261.
Ref 3	DARS-AS1 recruits METTL3/METTL14 to bind and enhance DARS mRNA m(6)A modification and translation for cytoprotective autophagy in cervical cancer. RNA Biol. 2022 Jan;19(1):751-763. doi: 10.1080/15476286.2022.2079889.
Ref 4	YTHDF2 interference suppresses the EMT of cervical cancer cells and enhances cisplatin chemosensitivity by regulating AXIN1. Drug Dev Res. 2022 Apr 30. doi: 10.1002/ddr.21942. Online ahead of print.
Ref 5	N(6)-methyladenosine modification of CENPK mRNA by ZC3H13 promotes cervical cancer stemness and chemoresistance. Mil Med Res. 2022 Apr 14;9(1):19. doi: 10.1186/s40779-022-00378-z.
Ref 6	Clinical pipeline report, company report or official report of ImmuneOncia Therapeutics.
Ref 7	YTHDF1 Aggravates the Progression of Cervical Cancer Through m(6)A-Mediated Up-Regulation of RANBP2. Front Oncol. 2021 Mar 19;11:650383. doi: 10.3389/fonc.2021.650383. eCollection 2021.
Ref 8	The pharmacogenetics of methotrexate. Rheumatology (Oxford). 2007 Oct;46(10):1520-4. doi: 10.1093/rheumatology/kem147. Epub 2007 Jun 24.
Ref 9	Recognition of RNA N(6)-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat Cell Biol. 2018 Mar;20(3):285-295. doi: 10.1038/s41556-018-0045-z. Epub 2018 Feb 23.
Ref 10	N(6)-Methyladenosine Associated Silencing of miR-193b Promotes Cervical Cancer Aggressiveness by Targeting CCND1. Front Oncol. 2021 Jun 10;11:666597. doi: 10.3389/fonc.2021.666597. eCollection 2021.
Ref 11	2-methoxyestradiol inhibits hypoxia-inducible factor 1alpha, tumor growth, and angiogenesis and augments paclitaxel efficacy in head and neck squamous cell carcinoma. Clin Cancer Res. 2004 Dec 15;10(24):8665-73. doi: 10.1158/1078-0432.CCR-04-1393.
Ref 12	N(6)-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification. Cell Death Dis. 2020 Oct 24;11(10):911. doi: 10.1038/s41419-020-03071-y.
Ref 13	Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75. doi: 10.1097/00008571-200309000-00005.
Ref 14	The m(6)A eraser FTO facilitates proliferation and migration of human cervical cancer cells. Cancer Cell Int. 2019 Dec 2;19:321. doi: 10.1186/s12935-019-1045-1. eCollection 2019.
Ref 15	Buprenorphine in cancer pain. Support Care Cancer. 2005 Nov;13(11):878-87. doi: 10.1007/s00520-005-0849-9. Epub 2005 Jul 12.
Ref 16	Oxidation of xenobiotics by recombinant human cytochrome P450 1B1. Drug Metab Dispos. 1997 May;25(5):617-22.
Ref 17	Possible involvement of P-glycoprotein in renal excretion of pazufloxacin in rats. Eur J Pharmacol. 2004 Oct 6;501(1-3):151-9.
Ref 18	Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63. doi: 10.1517/14728210902771334.
Ref 19	m(6)A methyltransferase METTL3-mediated lncRNA FOXD2-AS1 promotes the tumorigenesis of cervical cancer. Mol Ther Oncolytics. 2021 Jul 21;22:574-581. doi: 10.1016/j.omto.2021.07.004. eCollection 2021 Sep 24.
Ref 20	Long noncoding RNA GAS5-AS1 suppresses growth and metastasis of cervical cancer by increasing GAS5 stability. Am J Transl Res. 2019 Aug 15;11(8):4909-4921. eCollection 2019.
Ref 21	FTO-stabilized lncRNA HOXC13-AS epigenetically upregulated FZD6 and activated Wnt/Beta-catenin signaling to drive cervical cancer proliferation, invasion, and EMT. J BUON. 2021 Jul-Aug;26(4):1279-1291.
Ref 22	Long Noncoding RNA KCNMB2-AS1 Stabilized by N(6)-Methyladenosine Modification Promotes Cervical Cancer Growth Through Acting as a Competing Endogenous RNA. Cell Transplant. 2020 Jan-Dec;29:963689720964382. doi: 10.1177/0963689720964382.
Ref 23	ZFAS1 Exerts an Oncogenic Role via Suppressing miR-647 in an m(6)A-Dependent Manner in Cervical Cancer. Onco Targets Ther. 2020 Nov 17;13:11795-11806. doi: 10.2147/OTT.S274492. eCollection 2020.
Ref 24	IGF2BP2-modified circular RNA circARHGAP12 promotes cervical cancer progression by interacting m(6)A/FOXM1 manner. Cell Death Discov. 2021 Aug 14;7(1):215. doi: 10.1038/s41420-021-00595-w.
Ref 25	New hope for dry AMD?. Nat Rev Drug Discov. 2013 Jul;12(7):501-2. doi: 10.1038/nrd4038.
Ref 26	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 27	Cellular phototoxicity evoked through the inhibition of human ABC transporter ABCG2 by cyclin-dependent kinase inhibitors in vitro. Pharm Res. 2009 Feb;26(2):449-58. doi: 10.1007/s11095-008-9738-5. Epub 2008 Oct 9.
Ref 28	Role of cytochrome P450 in estradiol metabolism in vitro. Acta Pharmacol Sin. 2001 Feb;22(2):148-54.
Ref 29	Clinical pipeline report, company report or official report of Silicon Therapeutics.
Ref 30	The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. Br J Dermatol. 2002 Jul;147(1):20-31. doi: 10.1046/j.1365-2133.2002.04834.x.
Ref 31	Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an Ophthalmic Solution for Treating Dry Eye. ACS Med Chem Lett. 2012 Jan 31;3(3):203-6. doi: 10.1021/ml2002482. eCollection 2012 Mar 8.
Ref 32	Glutamine 161 of Glut1 glucose transporter is critical for transport activity and exofacial ligand binding. J Biol Chem. 1994 Aug 12;269(32):20533-8.
Ref 33	The xenobiotic inhibitor profile of cytochrome P4502C8. Br J Clin Pharmacol. 2000 Dec;50(6):573-80. doi: 10.1046/j.1365-2125.2000.00316.x.
Ref 34	P-glycoprotein (ABCB1) transports the primary active tamoxifen metabolites endoxifen and 4-hydroxytamoxifen and restricts their brain penetration. J Pharmacol Exp Ther. 2011 Jun;337(3):710-7.
Ref 35	The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46. doi: 10.1016/j.scitotenv.2007.02.021. Epub 2007 May 11.
Ref 36	2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles. Bioorg Med Chem Lett. 2010 Jan 15;20(2):679-83. doi: 10.1016/j.bmcl.2009.11.060. Epub 2009 Nov 20.
Ref 37	Alectinib (CH5424802) antagonizes ABCB1- and ABCG2-mediated multidrug resistance in vitro, in vivo and ex vivo. Exp Mol Med. 2017 Mar 17;49(3):e303. doi: 10.1038/emm.2016.168.
Ref 38	ARG098, a novel anti-human Fas antibody, suppresses synovial hyperplasia and prevents cartilage destruction in a severe combined immunodeficient-HuRAg mouse model. BMC Musculoskeletal Disorders 2010,11:221.
Ref 39	Transcriptional regulation of type 11 17Beta-hydroxysteroid dehydrogenase expression in prostate cancer cells. Mol Cell Endocrinol. 2011 Jun 6;339(1-2):45-53. doi: 10.1016/j.mce.2011.03.015. Epub 2011 Apr 28.