The c-MYC transcription factor conduces to resistance to cisplatin by regulating MMS19 in bladder cancer cells

Abstract

Chemoresistance is one of the dominant causes for tumor progression and recurrence of bladder cancer (BC). This paper investigated the effects of transcription factor c-MYC through promoting MMS19 expression on proliferation, metastasis and cisplatin (DDP) resistance in BC cells. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were applied to acquire the needed BC gene data. The mRNA and protein levels of c-MYC and MMS19 were verified with q-PCR or Western blot assay. MTT and Transwell assays were utilized to detect cell viability and metastasis. Chromatin Immunoprecipitation (ChIP) assay and Luciferase reporter assay were exerted to confirm the relationship between c-MYC and MMS19. TCGA and GEO BC datasets results implied MMS19 could be an independent indicator for BC patients’ prognosis. MMS19 expression was dramatically augmented in BC cell lines. Overexpression of MMS19 conduced to accelerate BC cells proliferation, metastasis and increase DDP resistance. c-MYC was positively correlated with MMS19 and acted as a transcription activator for MMS19 in BC cell lines and activated MMS19 expression. Overexpression of c-MYC facilitated BC cells proliferation, metastasis and DDP resistance. In conclusions, c-MYC gene was a transcriptional regulator of MMS19. Up-regulation of c-MYC facilitated BC cells proliferation, metastasis and DDP resistance by motivating MMS19 expression. This molecular mechanism between c-MYC and MMS19 exerts a crucial mission in BC tumorigenesis and DDP resistance, and may contribute to the diagnosis and therapy of BC for the time to come.