MiR-34a-5p suppresses the invasion and metastasis of liver cancer by targeting the transcription factor YY1 to mediate MYCT1 upregulation

Abstract

BackgroundIn recent years, microRNAs (miRNAs) are reported to act as molecular biomarkers for cancer diagnosis, treatment, and prognosis (including liver cancer) and to be involved in the development and progression of cancer and other physiological and pathological changes. However, the role of miR-34a-5p in liver cancer is still largely unknown. MethodsIn our study, the expression of miR-34a-5p in liver cancer tissues and HCC cell lines was detected by qRT-PCR. The CCK-8, scratch wound-healing motility and Transwell assays were used to evaluate the effect on cell proliferation, migration and invasion. The expression of YY1, E-cadherin, N-cadherin and vimentin was analysed by western blotting. The dual luciferase assay was performed to confirm whether YY1 is a target of miR-34a-5p. The combination of YY1 and MYCT1 was detected by chromatin immunoprecipitation (ChIP) assay. ResultsThe results showed that miR-34a-5p was downregulated in liver cancer tissues and HCC cell lines. Overexpression of miR-34a-5p inhibited the proliferation, migration and invasion of liver cancer cells. YY1 was a direct target of miR-34a-5p, and the expression of YY1 could reverse the influence of miR-34a-5p on the proliferation, migration and invasion of liver cancer cells. YY1 inhibited MYCT1 expression by directly binding to its promoter region, and knockdown of MYCT1 reversed the influence of miR-34a-5p on the proliferation, migration and invasion of liver cancer cells. ConclusionOur results suggest that miR-34a-5p could inhibit the invasion and metastasis of hepatoma cells by targeting YY1-mediated MYCT1 transcriptional repression.