Name	Thyroid Cancer
ICD	ICD-11: 2D10

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	FTO acts as a tumor suppressor to inhibit tumor glycolysis in Papillary thyroid cancer(PTC). FTO/Apolipoprotein E (APOE) axis inhibits PTC glycolysis by modulating IL-6/JAK2/STAT3 signaling pathway.
Responsed Disease	Papillary thyroid cancer [ICD-11: 2D10.1]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
Pathway Response	JAK-STAT signaling pathway			hsa04630
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	TPC-1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
	Nthy-ori 3-1	Normal	Homo sapiens	CVCL_2659
	K1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_2537
	IHH-4	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_2960
	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	Silence of METTL3 inhibited migratory ability and Wnt activity in TPC-1 cells. METTL3 positively regulated the enrichment abundance of Hepatocyte nuclear factor 1-alpha (HNF1A/TCF1) in anti-IGF2BP2. TCF1 was responsible for METTL3-regulated thyroid carcinoma progression via the m6A methylation.
Responsed Disease	Thyroid Cancer [ICD-11: 2D10]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Cell migratory
In-vitro Model	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153
	Nthy-ori 3-1	Normal	Homo sapiens	CVCL_2659
	TPC-1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	Silence of METTL3 inhibited migratory ability and Wnt activity in TPC-1 cells. METTL3 positively regulated the enrichment abundance of Hepatocyte nuclear factor 1-alpha (HNF1A/TCF1) in anti-IGF2BP2. TCF1 was responsible for METTL3-regulated thyroid carcinoma progression via the m6A methylation.
Responsed Disease	Thyroid Cancer [ICD-11: 2D10]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Cell migratory
In-vitro Model	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153
	Nthy-ori 3-1	Normal	Homo sapiens	CVCL_2659
	TPC-1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	Metalloreductase STEAP2 (STEAP2) overexpression inhibited papillary thyroid cancer cell proliferation, migration, and invasion in vitro and inhibited lung metastasis and tumorigenicity in vivo. METTL3 stabilized STEAP2 mRNA and regulated STEAP2 expression positively in an m6A-dependent manner.
Responsed Disease	Papillary thyroid cancer [ICD-11: 2D10.1]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hedgehog signaling pathway			hsa04340
Cell Process	Epithelial-to-mesenchymal transition
	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	TPC-1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
	KTC-1	Thyroid carcinoma	Homo sapiens	CVCL_6300
	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153
In-vivo Model	BCPAP cells (5×106) were introduced into the mice by means of subcutaneous injection through the flank area. STEAP2-saRNA or NC-saRNA (n = 6 for each group) was given by intratumoral multipoint injection at an interval of 3 days (5 injections in total) using an in vivo transfection reagent (Entranster -in vivo, Engreen, China) as per the vendor-provided protocol. Tumor volume (V) was monitored and calculated as follows: V = (L×W2)/2. For the in vivo tumor metastasis assay, BCPAP cells (5×106 cells) were administrated into mice through the tail vein. STEAP2-saRNA or NC-saRNA (n = 6 for each group) was given via tail vein injection at an interval of 3 days (8 injections in total).

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	METTL3 played a pivotal tumor-suppressor role in papillary thyroid cancer carcinogenesis through Proto-oncogene c-Rel (c-Rel) and RelA inactivation of the nuclear factor Kappa-B (NF-Kappa-B) pathway by cooperating with YTHDF2 and altered TAN infiltration to regulate tumor growth.
Responsed Disease	Papillary thyroid cancer [ICD-11: 2D10.1]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
In-vitro Model	TPC-1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
	Nthy-ori 3-1	Normal	Homo sapiens	CVCL_2659
	KTC-1	Thyroid carcinoma	Homo sapiens	CVCL_6300
	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153
In-vivo Model	For xenograft models, 5 × 106 BCPAP or KTC-1 cells from each group were injected subcutaneously into the flanks of female BALB/c nude mice (4-6 weeks old, Shanghai SLAC Laboratory Animal, China, n = 5 per group) in a volume of 150 uL PBS. Tumor growth was measured with a digital caliper every 4 days and calculated using the following formula: (length × width2)/2. To study the effect of IL-8 on tumor growth in vivo, scramble or shMETTL3 BCPAP cells were implanted hypodermically into BALB/c nude mice (2 × 106 cells in 150 uL PBS, n = 10 per group). When palpable tumors formed on day 14, mice were treated with DMSO or the IL-8 inhibitor SB225002 (10 mg/kg) by intraperitoneal injection 3 times per week for 3 weeks. Six weeks post-injection, the mice were sacrificed, and the tumors were collected to analyze the frequency of TANs by flow cytometry. For the lung metastasis model, BCPAP and KTC-1 cells (2 × 106 cells in 100 uL PBS) with the corresponding vectors were injected into the tail veins of BALB/c nude mice. Eight weeks after injection, the mice were euthanized, and metastatic lung nodules were analyzed (n = 5 for each group).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	METTL3 played a pivotal tumor-suppressor role in papillary thyroid cancer carcinogenesis through Proto-oncogene c-Rel (c-Rel) and RelA inactivation of the nuclear factor Kappa-B (NF-Kappa-B) pathway by cooperating with YTHDF2 and altered TAN infiltration to regulate tumor growth.
Responsed Disease	Papillary thyroid cancer [ICD-11: 2D10.1]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
In-vitro Model	TPC-1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
	Nthy-ori 3-1	Normal	Homo sapiens	CVCL_2659
	KTC-1	Thyroid carcinoma	Homo sapiens	CVCL_6300
	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153
In-vivo Model	For xenograft models, 5 × 106 BCPAP or KTC-1 cells from each group were injected subcutaneously into the flanks of female BALB/c nude mice (4-6 weeks old, Shanghai SLAC Laboratory Animal, China, n = 5 per group) in a volume of 150 uL PBS. Tumor growth was measured with a digital caliper every 4 days and calculated using the following formula: (length × width2)/2. To study the effect of IL-8 on tumor growth in vivo, scramble or shMETTL3 BCPAP cells were implanted hypodermically into BALB/c nude mice (2 × 106 cells in 150 uL PBS, n = 10 per group). When palpable tumors formed on day 14, mice were treated with DMSO or the IL-8 inhibitor SB225002 (10 mg/kg) by intraperitoneal injection 3 times per week for 3 weeks. Six weeks post-injection, the mice were sacrificed, and the tumors were collected to analyze the frequency of TANs by flow cytometry. For the lung metastasis model, BCPAP and KTC-1 cells (2 × 106 cells in 100 uL PBS) with the corresponding vectors were injected into the tail veins of BALB/c nude mice. Eight weeks after injection, the mice were euthanized, and metastatic lung nodules were analyzed (n = 5 for each group).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	Silencing METTL3 suppresses miR-222-3p expression and thus stimulates Serine/threonine-protein kinase 4 (STK4) expression, thereby repressing the malignancy and metastasis of Thyroid Carcinoma.
Responsed Disease	Thyroid Cancer [ICD-11: 2D10]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	METTL3 played a pivotal tumor-suppressor role in papillary thyroid cancer carcinogenesis through c-Rel and Transcription factor p65 (RELA) inactivation of the nuclear factor Kappa-B (NF-Kappa-B) pathway by cooperating with YTHDF2 and altered TAN infiltration to regulate tumor growth.
Responsed Disease	Papillary thyroid cancer [ICD-11: 2D10.1]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
In-vitro Model	TPC-1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
	Nthy-ori 3-1	Normal	Homo sapiens	CVCL_2659
	KTC-1	Thyroid carcinoma	Homo sapiens	CVCL_6300
	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153
In-vivo Model	For xenograft models, 5 × 106 BCPAP or KTC-1 cells from each group were injected subcutaneously into the flanks of female BALB/c nude mice (4-6 weeks old, Shanghai SLAC Laboratory Animal, China, n = 5 per group) in a volume of 150 uL PBS. Tumor growth was measured with a digital caliper every 4 days and calculated using the following formula: (length × width2)/2. To study the effect of IL-8 on tumor growth in vivo, scramble or shMETTL3 BCPAP cells were implanted hypodermically into BALB/c nude mice (2 × 106 cells in 150 uL PBS, n = 10 per group). When palpable tumors formed on day 14, mice were treated with DMSO or the IL-8 inhibitor SB225002 (10 mg/kg) by intraperitoneal injection 3 times per week for 3 weeks. Six weeks post-injection, the mice were sacrificed, and the tumors were collected to analyze the frequency of TANs by flow cytometry. For the lung metastasis model, BCPAP and KTC-1 cells (2 × 106 cells in 100 uL PBS) with the corresponding vectors were injected into the tail veins of BALB/c nude mice. Eight weeks after injection, the mice were euthanized, and metastatic lung nodules were analyzed (n = 5 for each group).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	METTL3 played a pivotal tumor-suppressor role in papillary thyroid cancer carcinogenesis through c-Rel and Transcription factor p65 (RELA) inactivation of the nuclear factor Kappa-B (NF-Kappa-B) pathway by cooperating with YTHDF2 and altered TAN infiltration to regulate tumor growth.
Responsed Disease	Papillary thyroid cancer [ICD-11: 2D10.1]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
In-vitro Model	TPC-1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
	Nthy-ori 3-1	Normal	Homo sapiens	CVCL_2659
	KTC-1	Thyroid carcinoma	Homo sapiens	CVCL_6300
	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153
In-vivo Model	For xenograft models, 5 × 106 BCPAP or KTC-1 cells from each group were injected subcutaneously into the flanks of female BALB/c nude mice (4-6 weeks old, Shanghai SLAC Laboratory Animal, China, n = 5 per group) in a volume of 150 uL PBS. Tumor growth was measured with a digital caliper every 4 days and calculated using the following formula: (length × width2)/2. To study the effect of IL-8 on tumor growth in vivo, scramble or shMETTL3 BCPAP cells were implanted hypodermically into BALB/c nude mice (2 × 106 cells in 150 uL PBS, n = 10 per group). When palpable tumors formed on day 14, mice were treated with DMSO or the IL-8 inhibitor SB225002 (10 mg/kg) by intraperitoneal injection 3 times per week for 3 weeks. Six weeks post-injection, the mice were sacrificed, and the tumors were collected to analyze the frequency of TANs by flow cytometry. For the lung metastasis model, BCPAP and KTC-1 cells (2 × 106 cells in 100 uL PBS) with the corresponding vectors were injected into the tail veins of BALB/c nude mice. Eight weeks after injection, the mice were euthanized, and metastatic lung nodules were analyzed (n = 5 for each group).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[9]
Response Summary	IGF2BP2 loss inhibited cell proliferation, migration and invasion, and induced cell apoptosis and cell cycle arrest by down-regulating HOXD antisense growth-associated long non-coding RNA (HAGLR) expression in an m6A-dependent manner in thyroid cancer cells.
Responsed Disease	Thyroid Cancer [ICD-11: 2D10]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
	Cell cycle progression
In-vitro Model	TPC-1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	Silencing METTL3 suppresses hsa-miR-222-3p expression and thus stimulates STK4 expression, thereby repressing the malignancy and metastasis of Thyroid Carcinoma.
Responsed Disease	Thyroid Cancer [ICD-11: 2D10]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation

Ref 1	FTO suppresses glycolysis and growth of papillary thyroid cancer via decreasing stability of APOE mRNA in an N6-methyladenosine-dependent manner. J Exp Clin Cancer Res. 2022 Jan 28;41(1):42. doi: 10.1186/s13046-022-02254-z.
Ref 2	Progression of Thyroid Carcinoma Is Promoted by the m6A Methyltransferase METTL3 Through Regulating m(6)A Methylation on TCF1. Onco Targets Ther. 2020 Feb 21;13:1605-1612. doi: 10.2147/OTT.S234751. eCollection 2020.
Ref 3	Involvement of breast cancer resistance protein (ABCG2) in the biliary excretion mechanism of fluoroquinolones. Drug Metab Dispos. 2007 Oct;35(10):1873-9. doi: 10.1124/dmd.107.014969. Epub 2007 Jul 16.
Ref 4	METTL3-mediated m6A modification of STEAP2 mRNA inhibits papillary thyroid cancer progress by blocking the Hedgehog signaling pathway and epithelial-to-mesenchymal transition. Cell Death Dis. 2022 Apr 18;13(4):358. doi: 10.1038/s41419-022-04817-6.
Ref 5	METTL3 restrains papillary thyroid cancer progression via m(6)A/c-Rel/IL-8-mediated neutrophil infiltration. Mol Ther. 2021 May 5;29(5):1821-1837. doi: 10.1016/j.ymthe.2021.01.019. Epub 2021 Jan 21.
Ref 6	Reduction of sulfamethoxazole and dapsone hydroxylamines by a microsomal enzyme system purified from pig liver and pig and human liver microsomes. Life Sci. 2005 May 27;77(2):205-19. doi: 10.1016/j.lfs.2004.12.028. Epub 2005 Feb 8.
Ref 7	METTL3-Induced miR-222-3p Upregulation Inhibits STK4 and Promotes the Malignant Behaviors of Thyroid Carcinoma Cells. J Clin Endocrinol Metab. 2022 Jan 18;107(2):474-490. doi: 10.1210/clinem/dgab480.
Ref 8	Transport of amino acid esters and the amino-acid-based prodrug valganciclovir by the amino acid transporter ATB(0,+). Pharm Res. 2004 Jul;21(7):1303-10. doi: 10.1023/b:pham.0000033019.49737.28.
Ref 9	IGF2BP2 knockdown suppresses thyroid cancer progression by reducing the expression of long non-coding RNA HAGLR. Pathol Res Pract. 2021 Sep;225:153550. doi: 10.1016/j.prp.2021.153550. Epub 2021 Jul 13.
Ref 10	Discovery and characterization of olokizumab: a humanized antibody targeting interleukin-6 and neutralizing gp130-signaling. MAbs. 2014 May-Jun;6(3):774-82. doi: 10.4161/mabs.28612. Epub 2014 Apr 2.
Ref 11	US patent application no. 6,498,035, Antisense modulation of MEKK3 expression.
Ref 12	A nonpromoting phorbol from the samoan medicinal plant Homalanthus nutans inhibits cell killing by HIV-1. J Med Chem. 1992 May 29;35(11):1978-86. doi: 10.1021/jm00089a006.
Ref 13	Clinical pipeline report, company report or official report of ESSA Pharma.
Ref 14	The manganese superoxide dismutase mimetic, M40403, protects adult mice from lethal total body irradiation. Free Radic Res. 2010 May;44(5):529-40. doi: 10.3109/10715761003649578.
Ref 15	Potent and selective PPAR-alpha agonist LY518674 upregulates both ApoA-I production and catabolism in human subjects with the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2009 Jan;29(1):140-6. doi: 10.1161/ATVBAHA.108.171223. Epub 2008 Nov 6.
Ref 16	An in vitro evaluation of guanfacine as a substrate for P-glycoprotein. Neuropsychiatr Dis Treat. 2011;7:501-5.
Ref 17	FDA Label of Vosevi. The 2020 official website of the U.S. Food and Drug Administration.
Ref 18	Interaction of the breast cancer resistance protein with plant polyphenols. Biochem Biophys Res Commun. 2004 Apr 23;317(1):269-75.