HOXA1 promotes proliferation and metastasis of bladder cancer by enhancing SMAD3 transcription.

ABSTRACT

BACKGROUND: Recent studies showed that HOXA1 can promote or suppress the transcription of target genes via binding to their promoter region, therefore regulating the development and progression of various cancers. However, the biological function of HOXA1 in bladder cancer (Bca) remains unknown. METHODS: qRT-PCR and Western blot assay was performed to measure the mRNA protein level of HOXA1 in Bca cells. CCK-8 and cell colony formation assay were carried out to detect cell proliferation ability. Wound healing assay was applied to detect cell migration ability, while transwell assay was applied to detect cell invasion ability. Chromatin Immunoprecipitation (ChIP) and dual-luciferase reporter assay were used to investigate the molecular mechanisms underlying HOXA1. RESULTS: In this study, we discovered that HOXA1 mRNA and protein was dramatically increased in Bca tissues and cells compared to matched normal tissues and normal bladder epithelial cell. Enhanced HOXA1 expression was positively correlated with bigger tumor size and lymphatic metastasis, causing shorter overall survival to Bca patients. Knockdown of HOXA1 obviously impaired cell proliferation and metastasis ability. Further experiments proved that HOXA1 could strength the transcription of SMAD3 via binding to the promoter region of SMAD3. CONCLUSION: In conclusion, our study suggested that HOXA1 contributed to the growth and metastasis of Bca and it might serve as a tumor biomarker for Bca treatment and prognosis monitoring.