MiR-124 changes the sensitivity of lung cancer cells to cisplatin through targeting STAT3

M.-M. Qi, F. Ge, X.-J. Chen, C. Tang, J. Ma

School of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, China. 718171345@qq.com

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• Oncology

OBJECTIVE: To investigate the role of micro ribonucleic acid (miR)-124 in drug resistance of non-small cell lung cancer (NSCLC), and to explore its underlying mechanism.
MATERIALS AND METHODS: The expression levels of miR-124 and signal transducer and activator of transcription 3 (STAT3) in maternal A549 cells and cisplatin-resistant A549/DDP cells were detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. A549 and A549/DDP cells were transfected with miR-124 mimics and miR-124 negative control (NC), respectively. Changes in the expression of STAT3 were detected via qRT-PCR and Western blotting. Meanwhile, the sensitivity of cells transfected with miR-124 mimics to cisplatin was detected via methyl thiazolyl tetrazolium (MTT) assay. The effects of miR-124 on the apoptosis, invasion and metastasis of cells were detected via flow cytometry, wound healing assay and transwell assay, respectively. Moreover, wild-type and mutant-type STAT3 luciferase reporter plasmids were co-transfected with miR-124 mimics or miR-124 NC. Luciferase activity was analyzed using the dual-luciferase reporter gene assay.
RESULTS: QRT-PCR and Western blotting revealed that the expression level of miR-124 in A549/DDP cells was significantly lower than that of A549 cells. However, the expression level of STAT3 in A549/DDP cells was significantly higher than that of A549 cells. Overexpression of miR-124 remarkably reduced the expression level of STAT3 in A549/DDP cells, increased the sensitivity of A549/DDP cells to cisplatin, and inhibited the invasion and metastasis capacities of cells. In addition, luciferase reporter gene assay demonstrated that miR-124 could negatively regulate the protein expression of STAT3 by binding to its 3’-untranslated region (UTR).
CONCLUSIONS: MiR-124 regulates the sensitivity of NSCLC to cisplatin. Moreover, it inhibits the invasion and metastasis capacities through targeting STAT3, which can serve as a therapeutic target for cisplatin-based chemotherapy resistance of NSCLC.

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