MiR‑139‑5p enhances cisplatin sensitivity in non‑small cell lung cancer cells by inhibiting cell proliferation and promoting apoptosis via the targeting of Homeobox protein Hox‑B2.

Abstract

The development of chemotherapeutic dug resistance hinders the clinical treatment of cancer. MicroRNAs (miRNAs/miRs) have been revealed to serve essential roles in the drug resistance of numerous types of cancer. miR-139-5p was previously reported to be associated with cisplatin (DDP) sensitivity in human nasopharyngeal carcinoma cells and colorectal cancer cells. However, the effect and underlying mechanism of miR-139-5p in DDP sensitivity in non-small cell lung cancer (NSCLC) cells has not yet been fully elucidated. In the present study, the expression of miR-139-5p and Homeobox protein Hox-B2 (HOXB2) in NSCLC tissues was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Subsequently, the effect of miR-139-5p on the DDP sensitivity of NSCLC cells in vitro was investigated. Cell proliferation was examined using a Cell Counting Kit-8 assay. Western blotting was used to evaluate the protein expression of HOXB2, phosphorylated (p)-PI3K, p-AKT, caspase-3 and cleaved-caspase-3, and RT-qPCR was used to evaluate the expression of miR-139-5p, and the mRNA expression levels of HOXB2, PI3K, AKT and caspase-3. The apoptotic rate of the cells was detected using flow cytometry. miR-139-5p expression in NSCLC tissues was shown to be significantly lower compared with that in adjacent tissues. Additionally, miR-139-5p increased cell apoptosis and inhibited NSCLC cell proliferation induced by DDP in vitro via modulating the PI3K/AKT/caspase-3 signaling pathway. Furthermore, HOXB2 was identified to be a target of miR-139-5p, and miR-139-5p was revealed to sensitize NSCLC cells to DDP via the targeting of HOXB2. Taken together, the results of the present study demonstrated that regulating the expression of miR-139-5p could provide a novel approach to reverse DDP resistance and increase chemosensitivity in the treatment of NSCLC.