J Gene Med. 2020 Sep 6:e3270. doi: 10.1002/jgm.3270. Online ahead of print.
BACKGROUND: The miRNA/histone deacetylase 9 (HDAC9) signaling axis has been reported to be involved in initiating and developing multiple malignant tumors. Herein, we aimed to determine whether miR-211-5p serves as a post-transcriptional regulator in bladder cancer (BCa) cell proliferation and apoptosis by targeting HDAC9.
METHODS: miRNA expression profiling of BCa tissues and para-carcinoma tissues was screened by miRNA microarray. After transfection with miR-211-5p mimics or short hairpin RNA of HDAC9 (sh-HDAC9), mRNA and protein expression was evaluated using quantitative reverse transcription-polymerase chain reaction and Western blotting, respectively. A bioinformatics algorithm was used, and a dual-luciferase reporter assay was performed to validate HDAC9 as a direct target of miR-211-5p. Cell proliferation was analyzed by the MTT assay. TUNEL staining was used to evaluate apoptosis in 5637 and T24 cells. The Transwell assay was used to assess migration and invasion.
RESULTS: miR-211-5p is downregulated in BCa tumor tissues and cell lines. miR-211-5p is identified as an independent biomarker for predicting overall survival. HDAC9 is a direct target of miR-211-5p, and overexpression of miR-211-5p represses HDAC9 protein expression in vitro. Overexpression of miR-211-5p or HDAC9 knockdown significantly inhibits proliferation, migration, and invasion of 5637 and T24 cells, as well as induces cell apoptosis.
CONCLUSION: miR-211-5p may play a role as a tumor suppressor and as a favourable prognostic marker in BCa.