Downregulation of miR‑138‑5p promotes non‑small cell lung cancer progression by regulating CDK8.

Abstract

Dysregulation of microRNAs (miRNAs) is frequently observed during cancer development. Aberrant expression of miRNA‑138‑5p (miR‑138‑5p) has been found in many types of cancer. However, the role and the mechanisms underlying miR‑138‑5p function in non‑small cell lung cancer (NSCLC) progression remain unknown. In the present study, miR‑138‑5p expression was identified to be decreased in tumor tissues compared with matched normal tissues from patients with NSCLC. In addition, low expression of miR‑138‑5p was detected in three NSCLC cell lines compared with a normal lung epithelium cell line. Moreover, CDK8 mRNA expression was increased in tumor tissues compared with matched normal tissues from patients with NSCLC, and an inverse association between miR‑138‑5p and CDK8 was observed. Furthermore, CDK8 was predicted to be a target of miR‑138‑5p. Dual luciferase assay confirmed that miR‑138‑5p could directly bind to the 3' untranslated region of CDK8 mRNA. In A549 cells, overexpression of miR‑138‑5p inhibited cell growth and significantly increased cell apoptosis rates and the number of cells in G0/G1 phase. Moreover, forced overexpression of CDK8 partially reversed miR‑138‑5p mimic‑induced cell growth arrest and alteration of cell apoptosis and cell cycle. In conclusion, the present results suggested that miR‑138‑5p may be a tumor suppressor in NSCLC cells and a promising therapeutic target for treating patients with NSCLC.