miR-451 selectively increases sensitivity to cisplatin in ERCC1-high non-small cell lung cancer cells.

Lung cancer is the leading cause of cancer-related death throughout the world and cisplatin chemoresistance is one of the major hindrances of efficiency in this malignancy therapy. It has been reported that miR-451, a tumor suppressor, is involved in sensitivity of cancer cells to cisplatin. However, the role of miR-451 in chemosensitivity of lung cancer cells and the underlying mechanism still remains to be not fully illuminated. We first assessed the expression of ERCC1 and miR-451 in six NSCLS cell lines and NHBE cells by qRT-PCR. Then ERCC1-low and ERCC1-high NSCLC cells were transfected with miR-451 mimic and mimic control. And cell viability, apoptotic cell rates, and migration activity was respectively measured by CCK-8 assay, flow cytometry, and wound healing assay. The expression of ERCC1, Wnt/β-catenin and PI3K/AKT pathway related factors were measured by western blot. The expression of miR-451 was higher in ERCC1-low NSCLC cells, while lower in ERCC1-high NSCLC cells. miR-451 overexpression inhibited the expression of ERCC1 in ERCC1-high NSCLC cells. Furthermore, miR-451 overexpression selectively enhanced cisplatin sensitivity in ERCC1-high NSCLC cells, as evidenced by reduction of cell viability with a dose manner. We further found that miR-451 overexpression significantly inhibited cell migration in ERCC1-high NSCLC cells. Interesting, Wnt/β-catenin and PI3K/AKT pathways were inhibited by miR-451 overexpression. This study demonstrates that miR-451 selectively promotes sensitivity to cisplatin in ERCC1-high NSCLC cells. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.