MicroRNA‑608 sensitizes non‑small cell lung cancer cells to cisplatin by targeting TEAD2.

Abstract

Cisplatin has been widely used as a conventional treatment for patients with non-small cell lung cancer (NSCLC). However, primary and acquired cisplatin resistances are frequently developed during the treatment of patients with NSCLC, leading to an increased mortality rate. Accumulating evidence demonstrated that aberrantly expressed microRNAs (miRs) are involved in the development of chemoresistance. In the present study, sensitivity of NSCLC cells to cisplatin was identified to increase following overexpression of miR-608. Conversely, sensitivity to cisplatin was reduced following miR-608 knockdown. Reverse transcription-quantitative PCR and western blotting analyses identified that TEA domain transcription factor 2 (TEAD2), a key regulator of cell stemness, was negatively regulated by miR-608 in NSCLC cells. By repressing TEAD2, miR-608 decreased the expression level of several target genes of the Hippo-yes-associated protein signaling pathway. Furthermore, TEAD2 mRNA was confirmed to be targeted by miR-608 in NSCLC cells via a dual-luciferase reporter assay. Importantly, the increased cisplatin sensitivity induced by miR-608 overexpression was reversed by transfection of TEAD2 in NSCLC cells. The present data suggested that miR-608 may represent a novel candidate biomarker for the evaluation of cisplatin sensitivity in patients with NSCLC.