m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05131
 [1], [2]
Non-coding RNA PCAT6 HNRNPA2B1  lncRNA       miRNA   circRNA Direct Enhancement m6A modification MIR222 MIR222 hnRNPA2B1 : m6A sites
m6A Modification:
m6A Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
m6A Target microRNA 222 (MIR222)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator Prostate cancer associated transcript 6 (PCAT6) LncRNA View Details
Regulated Target Heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) View Details
Crosstalk Relationship ncRNA  →  m6A Enhancement
Crosstalk Mechanism ncRNAs directly impacts m6A modification through recruiting m6A regulator
Crosstalk Summary Mechanically, PCAT6 functions as a scaffold between interferon-stimulated gene 15 (ISG15) and heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1), leading to ISGylation of hnRNPA2B1, thus protecting hnRNPA2B1 from ubiquitination-mediated proteasomal degradation.HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated hsa-miR-29a-3p, miR-29b-3p, and microRNA 222 (MIR222) and upregulated miR-1266-5p, miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Fulvestrant
 Drug Info 
Pathway Response TGF-beta signaling pathway hsa04350
Cell Process Endocrine-resistance
In-vitro Model
 MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF7/LCC9 Invasive breast carcinoma Homo sapiens CVCL_DP52
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
2C60: Breast cancer 2 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Entrectinib Approved [3]
Synonyms
1108743-60-7; RXDX-101; UNII-L5ORF0AN1I; Entrectinib (RXDX-101); L5ORF0AN1I; Benzamide, N-[5-[(3,5-difluorophenyl)methyl]-1H-indazol-3-yl]-4-(4-methyl-1-piperazinyl)-2-[(tetrahydro-2H-pyran-4-yl)amino]-; Benzamide, N-(5-((3,5-difluorophenyl)methyl)-1H-indazol-3-yl)-4-(4-methyl-1-piperazinyl)-2-((tetrahydro-2H-pyran-4-yl)amino)-; Entrectinib [USAN:INN]; YMX; Kinome_2659; Entrectinib(rxdx-101); Entrectinib (USAN/INN); SCHEMBL3512601; GTPL8290; CHEMBL1983268; KS-00000TSK
    Click to Show/Hide
External Link
CID: 25141092
TTD: D0O0LS
DrugBank: DB11986
 Compound Name Everolimus Approved [4]
External Link
CID: 6442177
TTD: D09ZSC
DrugBank: DB01590
References
Ref 1 HnRNPA2B1 ISGylation Regulates m6A-Tagged mRNA Selective Export via ALYREF/NXF1 Complex to Foster Breast Cancer Development. Adv Sci (Weinh). 2024 Jun;11(24):e2307639. doi: 10.1002/advs.202307639. Epub 2024 Apr 16.
Ref 2 HNRNPA2/B1 is upregulated in endocrine-resistant LCC9 breast cancer cells and alters the miRNA transcriptome when overexpressed in MCF-7 cells. Sci Rep. 2019 Jul 1;9(1):9430. doi: 10.1038/s41598-019-45636-8.
Ref 3 Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372... Cancer Discov. 2017 Apr;7(4):400-409.
Ref 4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015