MicroRNA-202 induces cell cycle arrest and apoptosis in lung cancer cells through targeting cyclin D1.

OBJECTIVE: MicroRNAs are critical regulators in tumorigenesis. This study is aimed at investigating the function of miR-202 in the proliferation of human lung cancer cells. PATIENTS AND METHODS: Lung cancer tissues and paired adjacent normal tissues were collected from 20 patients; the expression of miR-202 was tested by Realtime PCR; cell proliferation and cell cycle distribution were determined by CCK-8 assay and flow cytometry, respectively; apoptosis was determined by TUNEL assay and Western blot analysis of cleaved-PARP; the relationship between miR-202 and cyclin D1 mRNA 3'UTR was determined by luciferase activity assay. RESULTS: MiR-202 was significantly reduced in lung cancer tissues compared with the adjacent normal tissues. Overexpression of miR-202 inhibited cell proliferation and induced a G0/G1 cell cycle arrest and apoptosis. Luciferase activity assay and Western blot analysis together showed that miR-202 can bind to the 3'UTR of cyclin D1 mRNA directly and inhibits cyclin D1 expression at the protein level. In addition, restoration of cyclin D1 expression partially abolished cell cycle arrest and apoptosis induced by miR-202. CONCLUSIONS: MiR-202 is constantly downregulated in lung cancer and functions as a tumor suppressive gene via targeting cyclin D1. Modulating the level of miR-202 may be a novel therapeutic method for lung cancer.