MicroRNA-146a-5p induces cell cycle arrest and enhances apoptosis in gastric cancer via targeting CDC14A.

Abstract

Objective: The present study was designed to investigate the expression of miRNA-146a-5p in gastric cancer (GC) tissues and the paired nonmalignant counterparts, to explore the influences of miRNA-146a-5p on the cell biological behavior of MKN-28 cells (highly metastatic human gastric cancer cells), and to identify the function of abnormal expression of its target gene cell division cycle 14 homolog A (CDC14A) in GC. Methods: We detected the expression of miRNA-146a-5p in formalin-fixed and paraffin-embedded (FFPE) GC tissues through microarray and quantitative real-time polymerase chain reaction (qRT-PCR). Then, we employed cell counting kit-8 (CCK-8) assays, cell cycle assays, and apoptosis analysis to uncover the latent function of miRNA-146a-5p in MKN-28 human GC cells. We also validated the target of miRNA-146a-5p via luciferase reporter assays. Results: miRNA-146a-5p levels were examined in the majority of primary GC tissues and several GC cell lines. As a result, miRNA-146a-5p levels were significantly declined in the GC tissues and cells. In addition, miRNA-146a-5p demonstrated a straight act on its 3'-untranslated region (3'-UTR) of CDC14A mRNA, accordingly decreasing the contents of CDC14A mRNA as well as its protein expression. An inverse correlation between CDC14A and miRNA-146a-5p was observed. Conclusion: The data suggest miRNA-146a-5p may contribute to inducing cell cycle arrest as well as prompting GC cell apoptosis via directly targeting CDC14A. Therefore, miRNA-146a-5p may be a potential indicator of the occurrence and development of GC.