m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05147
 [1], [2]
Non-coding RNA PCAT6 HNRNPA2B1  lncRNA       miRNA   circRNA Direct Enhancement m6A modification ATG4B ATG4B hnRNPA2B1 : m6A sites
m6A Modification:
m6A Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
m6A Target Cysteine protease ATG4B (ATG4B)
 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.Overexpression of Cysteine protease ATG4B (ATG4B) rescued the malignancy driven by HNRNPA2B1 in breast cancer cells and increased the olaparib sensitivity. Our study revealed that the m6A reader HNRNPA2B1 mediated proliferation and autophagy in breast cancer cell lines by facilitating ATG4B mRNA decay and targeting HNRNPA2B1/m6A/ATG4B might enhance the olaparib sensitivity of breast cancer cells.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Olaparib
 Drug Info 
In-vitro Model
 MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-20 Invasive breast carcinoma of no special type Homo sapiens CVCL_0178
HCC1937 Breast ductal carcinoma Homo sapiens CVCL_0290
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
MCF-10A Normal Homo sapiens CVCL_0598
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 m(6)A reader HNRNPA2B1 destabilization of ATG4B regulates autophagic activity, proliferation and olaparib sensitivity in breast cancer. Exp Cell Res. 2023 Mar 1;424(1):113487. doi: 10.1016/j.yexcr.2023.113487. Epub 2023 Jan 21.
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