Regulatory effects of miRNA-19a on MAD2 expression and tumorigenesis in gastric cancer.

Abstract

MAD2 is a key mitotic checkpoint protein that when overexpressed provokes chromosomal instability in gastric cancer. In this work, we used in silico analysis in combination with in vitro studies and clinical data to explore if miRNAs can regulate MAD2 at post-transcriptional level. By in silico analysis, we discriminate the expression of miRNAs between tumor and normal tissue, finding miR-19a and miR-203 targeted to 3UTR MAD2L1. Luciferase Assays proved that those miRs are specific to MAD2L1 in human cells. RT-qPCR showed an inverse correlation between the expression miRNA19 and 203 and MAD2L1 in a panel of gastric cancer cell lines and in a pilot series of patients study. The miR-19a expression reduces the migration ability of AGS cells and invasion in MKN45 cells. Furthermore, the expression of the miRNA in combination with mitotic checkpoint drugs increase apoptosis. Finally, the TCGA analysis showed that Gastric Cancer patients with overexpression of MAD2, showed higher overall survival when miR-19a was overexpressed. Together, our results defined miR-19a as a critical regulator of MAD2 protein in Gastric Cancer and could potentially be used as a prognostic biomarker in clinical use.