MicroRNA-29b-3p reduces cisplatin resistance in non-small cell lung cancer by targeting myeloid cell leukemia-1

Introduction

Non-small cell lung cancer (NSCLC) is a heterogeneous series of tumors. Given the implication of microRNA-29b-3p (miR-29b-3p) in cisplatin resistance in NSCLC, this study expounded on the further mechanism.

Methods

A549 cells and cisplatin-resistant cells A549/DDP were selected. A549/DDP cells were manipulated with miR-29b-3p mimics/MCL-1 siRNA. miR-29b-3p and MCL levels were assessed. Cell sensitivity to cisplatin of different concentrations was examined by CCK-8. A549/DDP cell apoptosis under 10 µM cisplatin treatment was tested by flow cytometry. The targeted relationship between miR-29b-3p and MCL-1 was analyzed by TargetScan database and dual-luciferase assay. miR-29b-3p and MCL-1 were overexpressed to study whether miR-29b-3p regulated A549/DDP cell drug resistance by targeting MCL-1. To verify the effect of miR-29b-3p on DDP sensitivity in vivo, nude mice were subcutaneously injected with A549/DDP cells carrying the miR-29b-3p overexpressing lentiviral vector or the corresponding control vector to establish the nude mouse xenograft tumor model, and after 3 weeks, injected with DDP via tail vein for 2 weeks.

Results

miR-29b-3p level in A549/DDP cells was diminished and MCL-1 expression was raised. miR-29b-3p overexpression or MCL-1 silencing enhanced A549/DDP cell sensitivity to cisplatin by promoting apoptosis. miR-29b-3p targeted MCL-1. MCL-1 overexpression partially averted miR-29b-3p overexpression-promoted cisplatin sensitivity and apoptosis. Tumor volume/weight/MCL-1 level in the A549/DDP/miR mimics + DDP group were reduced, and miR-29b-3p was up-regulated versus the A549/DDP/mimics NC + DDP group. Overexpression of miR-29b-3p induced apoptosis in tumor tissues of NSCLC mice.

Conclusion

miR-29b-3p targeted MCL-1, thus promoting apoptosis and enhancing A549/DDP cell sensitivity to cisplatin.