Abstract
BackgroundMicroRNAs (miRs) are endogenous, single-stranded, non-coding RNAs that are involved in various physiological processes, development and the progression of various types of cancer. The role of miR-200a-3p in various types of cancer has been previously reported. The present study aimed to investigate the expression levels of miR-200a-3p in human bladder cancer, as well as its potential role in disease pathogenesis.MethodsIn vitro: Agilent miRNA microarray and QPCR analysis of miR-200a-3p expression in bladder cancer. Gene overexpression and interference technology analysis of the effects of miR-200a-3p and de-ubiquituination enzyme TNFα induced protein 3 (A20) on the function of bladder cancer cells; dual luciferase technology for promoter efficiency analysis; Animal experiments: Nude mice are used for tumor formation experiments, and the effects of genes on tumors are directly analyzed on animals;ResultsCompared with adjacent non-tumor tissues, miR-200a-3p expression levels were significantly upregulated in bladder cancer tissues. Moreover, increased miR-200a-3p expression was significantly associated with distant metastasis and advanced stage. In addition, compared with the miR-Negative control (NC) group, miR-200a-3p overexpression promoted bladder cancer cell proliferation, migration, invasion, cell cycle and release of inflammatory cytokines, but inhibited cell apoptosis. Mechanistically, de-ubiquituination enzyme TNFα induced protein 3 (A20) was identified as a target gene of miR-200a-3p in bladder cancer cell lines. An inverse association between miR-200a-3p expression and A20 expression in bladder cancer tissues and cell lines was also identified. A20 overexpression in miR-200a-3p-overexpression bladder cancer cells attenuated miR-200a-3p overexpression-mediated effects on cell proliferation, migration, apoptosis and cytokine production. Moreover, compared with the miR-NC group, miR-200a-3p overexpression significantly promoted tumor growth in vivo, and A20 overexpression blocked the promoting effect of miR-200a-3p on bladder cancer. ConclusionsThe results of the present study indicated that miR-200a-3p might serve as an oncogene in human bladder cancer by targeting a novel gene A20; therefore, miR-200a-3p and A20 might serve as novel therapeutic targets for bladder cancer.