m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05994
 [1]
Non-coding RNA lncSNHG5 IGF2BP2  lncRNA       miRNA   circRNA Direct Enhancement m6A modification ZNF281 ZNF281 IGF2BP2 : m6A sites
m6A Modification:
m6A Regulator Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) READER
 Regulator Info 
m6A Target Zinc finger protein 281 (ZNF281)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator Small nucleolar RNA host gene 5 (SNHG5) LncRNA View Details
Regulated Target Insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) View Details
Crosstalk Relationship ncRNA  →  m6A Enhancement
Crosstalk Mechanism ncRNAs directly impacts m6A modification through recruiting m6A regulator
Crosstalk Summary SNHG5 enhanced Zinc finger protein 281 (ZNF281) mRNA stability by binding with the m6A reader IGF2BP2. Enhanced ZNF281 transcriptionally regulated CCL2 and CCL5 expression to activate P38 MAPK signaling in endothelial cells. High CCL2 and CCL5 expression was associated with tumor metastasis and poor prognosis in BC patients. The inhibitors RS102895, marasviroc and cenicriviroc inhibited angiogenesis and vascular permeability in the PMN by blocking the binding of CCL2/CCR2 and CCL5/CCR5. The lncSNHG5-ZNF281-CCL2/CCL5 signaling axis plays an essential role in inducing premetastatic niche formation to promote BC metastasis.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Cenicriviroc
 Drug Info 
In-vitro Model
 MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
In-vivo Model MDA-MB-231 cells (1×106 cells/mouse) were mixed with an equivalent number of NFs/Ctrl, CAFs/shNC, CAFs/sh lncSNHG5, CAFs/shZNF281, CAFs/sh lncSNHG5/ZNF281, CAFs/RS102895, CAFs/Maraviroc or CAFs/Cenicriviroc in 200 l PBS:Matrigel at a ratio of 1:1.
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 [2]
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 [3]
External Link
CID: 6442177
TTD: D09ZSC
DrugBank: DB01590
References
Ref 1 Cancer-associated fibroblasts facilitate premetastatic niche formation through lncRNA SNHG5-mediated angiogenesis and vascular permeability in breast cancer. Theranostics. 2022 Oct 17;12(17):7351-7370. doi: 10.7150/thno.74753. eCollection 2022.
Ref 2 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 3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015