Downregulation of miR-3934-5p enhances A549 cell sensitivity to cisplatin by targeting TP53INP1.

Abstract

Tumor protein p53-inducible nuclear protein 1 (TP53INP1) is a tumor suppressor associated with malignant tumor metastasis. In addition, it has been reported that hsa-microRNA (miR)-3934 serves key roles in various types of lung cancer, including small-cell lung carcinomas (SCLC) and non-SCLC (NSCLC). Therefore, the present study aimed to determine the effects of miR-3934-5p on cell proliferation and apoptosis, and on sensitivity to cisplatin (DDP). Reverse transcription-quantitative polymerase chain reaction analysis and western blotting were conducted for the analysis of mRNA and protein expression, respectively. Furthermore, the target of miR-3934-5p was investigated using a luciferase reporter assay and apoptosis was analyzed by flow cytometry. The results demonstrated that miR-3934-5p was upregulated in NSCLC tissues and A549 cells. Increases in the half-maximal inhibitory concentration (IC50) and the expression of miR-3934-5p were observed in the A549/DDP group. miR-3934-5p mimic promoted the expression of miR-3934-5p and the IC50 of the A549 cells. miR-3934-5p inhibitor downregulated miR-3934-5p and reduced the IC50 of A549/DDP cells. miR-3934-5p was revealed to target the 3′-untranslated region of TP53INP1. The downregulation of miR-3934-5p significantly suppressed the proliferation and promoted the apoptosis of A549/DDP cells, which were reversed by transfection with TP53INP1 small interfering (si)RNA. The protein and mRNA expression levels of TP53INP1, B-cell lymphoma 2 (Bcl-2)-associated-X and p21 were significantly increased, whereas those of Bcl-2 were significantly decreased in the miR-3934-5p inhibitor group, which was significantly reduced by TP53INP1 siRNA transfection. miR-3934-5p, as a tumor suppressor in NSCLC, may promote the sensitivity of cells to DDP by targeting TP53INP1, associated with the suppression of cell proliferation and promotion of apoptosis.