The transcription factor MYB transcriptionally regulates MTFR2 to promote chemotherapy resistance of gastric cancer cells through DNA damage repair
Objective To investigate the effect and molecular mechanism of v-myb avian myeloblastosis viral on-cogene homolog(MYB)transcriptional regulation of mitochondrial fission regulator 2(MTFR2)on cisplatin(DDP)resistance in gastric cancer(GC)cells.Methods TCGA database was used to analyze the differential mRNAs in GC and predict its upstream regulatory molecules,qRT-PCR was used to detect the expression of MT-FR2 and MYB.Dual-luciferase and Chromatin Immunoprecipitation(ChIP)experiments was used to verify the regulatory relationship between MTFR2 and MYB.Cell Counting Kit-8(CCK-8)was used to detect the cell via-bility and calculate IC50 value.Flow cytometry was used to detect cell cycle and apoptosis.Comet assay was used to detect DNA damage,and protein immunoblotting was used to detect the expression of DNA damage-associated proteins(γ-H2AX,ATM,p-ATM).Results MTFR2 was significantly overexpressed in GC tissues and cells,and knockdown of MTFR2 reduced cell proliferation,blocked S phase,induced apoptosis,and promoted DNA damage and DDP sensitivity.Bioinformatics predicted the presence of the upstream transcription factor MYB in MTFR2,the expression of MYB was significantly upregulated in GC tissues and cells,and dual luciferase and ChIP verified the binding relationship between the MTFR2 promoter region and MYB.Response experiments re-vealed that further overexpression of MTFR2 was able to reverse the inhibitory effect of knockdown of MYB on GC cell proliferation and DDP resistance.Conclusion Upregulation of MTFR2 expression by MYB promotes GC cell proliferation and DDP resistance through the DNA damage pathway,suggesting that targeting the MYB/MTFR2 regulatory axis may be a potential pathway to overcome DDP resistance in GC.
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维普
