m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05629
 [1]
m6A modification hsa-miR-222-3p hsa-miR-222-3p METTL3 Methylation : m6A sites Direct Enhancement Non-coding RNA miR-222-3p STK4  lncRNA       miRNA   circRNA
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target hsa-miR-222-3p
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator hsa-miR-222-3p microRNA View Details
Regulated Target Serine/threonine-protein kinase 4 (STK4) View Details
Crosstalk Relationship m6A  →  ncRNA Enhancement
Crosstalk Mechanism m6A regulators directly modulate the functionality of ncRNAs through specific targeting ncRNA
Crosstalk Summary Silencing METTL3 suppresses hsa-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
 Disease Info 
Cell Process Cell proliferative
Cell migration
Cell invasion
In-vitro Model
 HEK293T Normal Homo sapiens CVCL_0063
TPC-1 Thyroid gland papillary carcinoma Homo sapiens CVCL_6298
SW579 Thyroid gland squamous cell carcinoma Homo sapiens CVCL_3603
In-vivo Model Forty-eight 4-week-old, specific pathogen-free female BALB/c nude mice (weighing 20-22 g),TPC-1 cells were subjected to 3 different treatments: transfection with sh-NC or sh-METTL3 + sh-NC or sh-METTL3 + sh-STK4. For the tumor formation model, 24 nude mice were randomly divided into 3 groups (8 mice/group). The aforementioned cell suspension of the 3 groups was diluted to a concentration of 1 × 107 cells/mL, and 0.2 mL of each group was subcutaneously administrated to the right groin of the nude mice for the development of xenografted tumors. Five weeks later, the mice were euthanized with an intraperitoneal injection of 40 mg/kg pentobarbital (Sigma) to collect the tumor tissues.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Serine/threonine-protein kinase 4 (STK4) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name TAT-120 Investigative [2]
Synonyms
MIP-120, Vasade; Peptide mammalian sterile 20-like kinase 1 inhibitors (ischemic heart disease); Peptide Mst-1 inhibitors (ischemia), Vasade; Peptide mammalian sterile 20-like kinase 1 inhibitors (ischemic heart disease), Vasade
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MOA Inhibitor
External Link
TTD: D0A7HY
2D10: Thyroid Cancer 12 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Lenvatinib Approved [3]
Synonyms
E 7080; E-7080, E7080; 4-[3-chloro-4-(cyclopropylcarbamoylamino)phenoxy]-7-methoxy-quinoline-6-carboxamide
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External Link
CID: 9823820
TTD: D0R0FO
DrugBank: DB09078
 Compound Name Cabozantinib Approved [4]
Synonyms
Cabometyx; Cometriq
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External Link
CID: 25102847
TTD: D0IQ6P
DrugBank: DB08875
 Compound Name Thyrotropin Alfa Approved [5]
External Link
TTD: D0H4TQ
 Compound Name Selpercatinib Approved [6]
Synonyms
MFOVQWYFURMVKU-IWAAJCSBSA-N; 2222755-14-6; LOXO292; ARRY-192; LOXO 292; EX-A2636
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External Link
CID: 134823904
TTD: D01KOA
 Compound Name Selumetinib Phase 3 [7]
Synonyms
AZD-6244; ARRY142886; AZD6244; AZD 6244; 6UH91I579U; ARRY 142886; ARRY-142886; AZD6244 (Selumetinib); AZD6244(Selumetinib); CHEBI:90227; CHEMBL1614701; MEK inhibitors; Selumetinib (AZD6244); UNII-6UH91I579U
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External Link
CID: 10127622
TTD: D0T5DP
DrugBank: DB11689
 Compound Name QGE-031 Phase 2 [8]
External Link
TTD: D0J7CH
 Compound Name GI-6207 Phase 2 [9]
External Link
TTD: D0L7VC
 Compound Name AIC100 Phase 1 [10]
External Link
TTD: DP0NU9
 Compound Name CYTO-403 Phase 1 [11]
External Link
TTD: DB2R5Y
 Compound Name Demogastrin Phase 1 [12]
Synonyms
Technetium-99m-Demogastrin 2; Cholecystokinin-2 receptor/gastrin-R binding radiolabeled minigastrinanalogue (medullary thyroid cancer), Biomedica Life Science; 99mTc-Demogastrin 2; 99mTc-N4-Gly-(D)Glu-(Glu)5-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2
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External Link
TTD: D0QJ6L
 Compound Name Recombinant TSH superagonists Investigative [13]
Synonyms
Recombinant TSH superagonists (thyroid cancer); TR-1401; TR-1402; Recombinant TSH superagonists (thyroid cancer), Trophogen; TSH superagonist (thyroid cancer/goiter), Trophogen; Thyroid stimulating hormone superagonist (thyroid cancer/goiter), Trophogen
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External Link
TTD: D0U2DY
 Compound Name ITRI-305 Investigative [14]
Synonyms
RET tyrosine kinase inhibitors, Industrial Technology Research Institute
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External Link
TTD: D0N5TB
References
Ref 1 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 2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2225).
Ref 3 FDA Approved Drug Products from FDA Official Website. 2018. Application Number: (ANDA) 208627.
Ref 4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5887).
Ref 5 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020898.
Ref 6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
Ref 7 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 8 ClinicalTrials.gov (NCT02336425) Efficacy and Safety of QGE031 Compared With Placebo in Patients Aged 18-75 Years With Asthma. U.S. National Institutes of Health.
Ref 9 ClinicalTrials.gov (NCT01856920) A Phase 2 Study of GI-6207 in Patients With Recurrent Medullary Thyroid Cancer. U.S. National Institutes of Health.
Ref 10 ClinicalTrials.gov (NCT04420754) Study of AIC100 in Relapsed/Refractory Thyroid Cancer. U.S. National Institutes of Health.
Ref 11 Clinical pipeline report, company report or official report of Cytocom
Ref 12 99mTc-Demogastrin 2 for CCK 2-receptor scintigraphy in medullary thyroid carcinoma. J Nucl Med. 2008; 49 (Supplement 1):115P.
Ref 13 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 255).
Ref 14 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2185).