Inhibition of miR-141 reverses cisplatin resistance in non-small cell lung cancer cells via upregulation of programmed cell death protein 4.

ABSTRACT

OBJECTIVE: MicroRNAs are a class of essential regulators in cancer, and previous studies have shown that miR-141 is a tumor suppressor in non-small cell lung cancer (NSCLC). However, it is still unknown whether it regulates chemosensitivity. We aimed to investigate the role of miR-141 in cisplatin resistance in NSCLC cells. MATERIALS AND METHODS: MiR-141 expression in A549 and A549/DDP cell lines have been quantified by real-time PCR. Protein level of PDCD4 and caspase-3 have been determined by Western blot analysis. Drug sensitivity and apoptosis have been determined by MTT assay and TUNEL assay, respectively. Luciferase activity assay was employed to validate the relationship between 3'UTR of PDCD4 mRNA and miR-141. RESULTS: We observed that miR-141 expression was significantly up-regulated in cisplatin-resistant A549/DDP cells compared with the parental cell line A549; and PDCD4, an important apoptosis regulator, was found to be down-regulated. Luciferase activity assay and Western blot analysis confirmed that PDCD4 is a direct target of miR-141. Inhibition of miR-141 in A549/DDP cells markedly increased cisplatin sensitivity and apoptosis, which was partially abrogated by PDCD4 inhibition, indicating that PDCD4 is a functional target of miR-141 in of the regulation of cisplatin sensitivity. CONCLUSIONS: Our data showed that miR-141 participates in regulating cisplatin sensitivity in non-small lung cancer cells via PDCD4 inhibition, and suppression of miR-141 might be a therapeutic method to overcome cisplatin resistance in clinical practice.