m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05322
 [1]
Non-coding RNA miR-16-5p YTHDF1  lncRNA       miRNA   circRNA Direct Inhibition m6A modification PKM PKM YTHDF1 : m6A sites
m6A Modification:
m6A Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
m6A Target Pyruvate kinase PKM (PKM2/PKM)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator hsa-miR-16-5p microRNA View Details
Regulated Target YTH domain-containing family protein 1 (YTHDF1) View Details
Crosstalk Relationship ncRNA  →  m6A Inhibition
Crosstalk Mechanism ncRNAs directly impacts m6A modification through modulating the expression level of m6A regulator
Crosstalk Summary tumor hypoxia can transcriptionally induce HIF1alpha and post-transcriptionally inhibit the expression of hsa-miR-16-5p to promote YTHDF1 expression, which could sequentially enhance tumor glycolysis by upregulating Pyruvate kinase PKM (PKM2/PKM) and eventually increase the tumorigenesis and metastasis potential of breast cancer cells.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response HIF-1 signaling pathway hsa04066
Cell Process Glycolysis
In-vivo Model To investigate the effect of YTHDF1 on breast cancer progression in mice, the reared mice were randomly divided into two groups (n = 5). Each mouse was injected subcutaneously with 5 × 106 units of tumor cells to construct the tumor model. In the shCtrl group, shCtrl-transfected 4T1 (ATCC, #CRL-2539) cells were injected subcutaneously into mice to construct YTHDF1-normal 4T1 tumors. To investigate the effect of miR-16-5p on breast cancer progression by regulating the expression of YTHDF1, three experimental groups (n = 5) were designed for the in vivo experiment, which were the agomiR-nc+antgomiR-nc, agomiR-16-5p + antgomiR-nc, and agomiR-16-5p + antgomiR-16-5p groups
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Pyruvate kinase PKM (PKM2/PKM) 2 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name CAP-232 Phase 2a [2]
Synonyms
TT-232; UNII-49D4Q4254Z; TT 232; 49D4Q4254Z; 147159-51-1; Phe-cys-tyr-trp-lys-cys-thr-NH2 (2-6)-disulfide; TLN 232; CAP 232; Phenylalanyl-cysteinyl-tyrosyl-tryptophyl-lysyl-cysteinyl-threoninamide (2-6)-disulfide; AC1OCF7X; CHEMBL539934; TLN-232; L-Threoninamide, D-phenylalanyl-L-cysteinyl-L-tyrosyl-D-tryptophyl-L-lysyl-L-cysteinyl-, cyclic (2-6)-disulfide; TT2-32; ZINC169289417; AKOS024458270; DB12088; NCGC00249606-01
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MOA Modulator
External Link
CID: 6918265
TTD: D09EFC
DrugBank: DB12088
 Compound Name TP-1454 Phase 1 [3]
MOA Activator
External Link
TTD: DLN0P8
2C60: Breast cancer 2 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Entrectinib Approved [4]
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
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External Link
CID: 25141092
TTD: D0O0LS
DrugBank: DB11986
 Compound Name Everolimus Approved [5]
External Link
CID: 6442177
TTD: D09ZSC
DrugBank: DB01590
References
Ref 1 YTHDF1 upregulation mediates hypoxia-dependent breast cancer growth and metastasis through regulating PKM2 to affect glycolysis. Cell Death Dis. 2022 Mar 23;13(3):258. doi: 10.1038/s41419-022-04711-1.
Ref 2 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics. 2005 Aug;86(2):127-41. doi: 10.1016/j.ygeno.2005.04.008.
Ref 3 Clinical pipeline report, company report or official report of Sumitomo Dainippon Pharma.
Ref 4 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 5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015