MicroRNA-218 regulates cisplatin (DPP) chemosensitivity in non-small cell lung cancer by targeting RUNX2.
Downregulation of microRNA-218 (miR-218) is found in various human cancers, including non-small cell lung cancer (NSCLC). However, the involvement of chemosensitivity to cisplatin (DDP) and the underlying molecular mechanism remain unclear. In this study, we investigate whether miR-218 mediates NSCLC cell functions associated with chemoresistance. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect miR-218 expression in NSCLC cell lines A549/DDP and/or A549. The cell activity was measured by MTT assay. Cell cycle and cell apoptosis were detected by flow cytometry. Luciferase reporter assays and Western blots were used to validate runt-related transcription factor 2 (RUNX2) as a direct target gene of miR-218. miR-218 was significantly reduced in A549/DDP cells compared with parent A549 cells. Upregulation of miR-218 altered cell cycle-induced cell apoptosis and enhanced the sensitivity of A549/DDP cells to cisplatin. Mechanistically, RUNX2 was identified as a direct and functional target of miR-218, and RUNX2 executed the former on lung cancer chemoresistance. Our present study demonstrated for the first time that downregulation of miR-218 may contribute to the chemoresistance of NSCLC cells to cisplatin, which leads to upregulation of RUNX2. Uncovering the mechanism represents a novel approach to enhance the efficacy of chemotherapy during cancer treatment.
Department of Nuclear, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
Jing
J
Xie
Department of Nuclear, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
Fei
F
Yu
Department of Nuclear, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
Dan
D
Li
Department of Nuclear, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
Xuchao
X
Zhu
Department of Nuclear, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China. zxpkxy@126.com.
Xiaoping
X
Zhang
Department of Nuclear, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China. nucleartj@163.com.
Zhongwei
http://orcid.org/0000-0001-9017-0385
Z
Lv
D000072283:A549 Cells / Q000187:drug effects; D000970:Antineoplastic Agents / Q000737:chemistry; D017209:Apoptosis; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D002945:Cisplatin / Q000737:chemistry*; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D060888:Real-Time Polymerase Chain Reaction
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D050659:Core Binding Factor Alpha 1 Subunit; C547471:MIRN218 microRNA, human; D035683:MicroRNAs; C493709:RUNX2 protein, human; D002945:Cisplatin
Chemosensitivity; Cisplatin (DDP); NSCLC; RUNX2; miR-218