The miR-142-5p overexpression induces cell cycle arrest and apoptosis by targeting genes MCL1 and CDK6 in pancreatic cancer cells; AsPC-1, PANC-1

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers worldwide, and there is an urgent demand for novel therapeutic approaches. MicroRNAs (miRNAs) are promising molecules to regulate gene expression in PDAC. This study investigates the role of miR-142 in cell proliferation and apoptosis in two cell lines, AsPC-1 and PANC-1, with a focus on gene expression changes of selected genes induced by overexpression of miR-142-5p. The molecular features in PDAC were evaluated using KEGG, and significant genes in cell cycle regulation, apoptosis, and PI3k/AKT pathway were selected (CDK6, MCL1, PIK3CA). DIANA-microT-CDS and TargetScan version 7.1 were used to select miR-142 based on prediction score. Selected genes did not contain any predicted seed site matches for the 3p arm of miR-142. miR-142 was overexpressed by transfecting a vector carrying the pre-miRNA-142 sequence into two pancreatic cancer cell lines. Overexpression of miR-142 and its effect on downregulating target genes was confirmed by quantitative real-time PCR (RT-qPCR). Predicted target genes (CDK6 and MCL1) were evaluated by the Luciferase assay. Apoptosis and cell cycle arrest were performed to analyze cell proliferation and cell viability under the effect of miR-142. Our results showed that miR-142-5p reduced the expression of its target genes. Cell cycle arrest was increased in both cell lines, while apoptosis increased in PANC-1. Overall, miR-142 may function as a tumor suppressor in PDAC by downregulating the overexpressed cancer-related genes and suppressing proliferation in AsPC-1 and PANC1.