Mir-126-5p Promotes Cisplatin Sensitivity of Non-Small-Cell Lung Cancer by Inhibiting ADAM9.

Abstract

Objective The aim of the study was to investigate molecular mechanisms underlying the role of miR-126-5p in cisplatin (DDP) sensitivity of non-small-cell lung cancer (NSCLC). Methods The expression of miR-126-5p and ADAM9 in NSCLC cancer tissues and adjacent tissues, cisplatin-sensitive and drug-resistant NSCLC patient tissues, human normal lung epithelial cells (BESA-2B), human lung adenocarcinoma cell lines A549 and H1560, and cisplatin-resistant mutant cell lines A549/DDP and H1560/DDP was detected by qRT-PCR. After overexpression of miR-126-5p or ADAM9 in A549/DDP and H1560/DDP, MTT and clone formation were used to detect the cell proliferation ability of each treatment group. Flow cytometry was used to detect changes in cell apoptosis. The protein expression of ADAM9 and key molecules of PTEN/PI3K/Akt pathways in cells was measured by western blot. Results Compared with NSCLC adjacent tissues and NSCLC cisplatin-sensitive tissues, miR-126-5p expression was downregulated in NSCLC tissues and cisplatin-resistant NSCLC tissues and ADAM9 was upregulated. qRT-PCR further detected that miR-126-5p was downregulated in A549, H1560, and their cisplatin-resistant strains A549/DDP and H1560/DDP, while ADAM9 was upregulated. Moreover, overexpression of miR-126-5p inhibited A549/DDP and H1560/DDP cell proliferation and promoted cell apoptosis. The results of dual luciferase showed that miR-126-5p targeted and negatively regulated ADAM9. We also found that overexpression of ADAM9 could reverse the effects of miR-126-5p on NSCLC cell proliferation, apoptosis, and cisplatin sensitivity, and this effect may be achieved by inhibiting the activity of the PTEN/PI3K/Akt signaling pathway. Conclusion Our data indicated that miR-126-5p may negatively regulate ADAM9 to promote the sensitivity of clinical DDP treatment of NSCLC and be a potential therapeutic target for NSCLC treatment.