MiR-873 acts as a novel sensitizer of glioma cells to cisplatin by targeting Bcl-2.
Treatment with cisplatin, a chemotherapeutic agent commonly used in glioma patients, often results in chemoresistance. Increasing evidence has shown that microRNAs (miRNAs) are implicated in the drug resistance of gliomas. However, the function of miR‑873 in cisplatin resistance of gliomas remains unknown. In this study, we found that many miRNAs, including miR‑873, are differentially expressed in cisplatin-resistant glioma cells compared to wild-type glioma cells. Moreover, cisplatin reduced the expression of miR‑873 in a time-dependent manner. Overexpression of miR‑873 decreased the cell proliferation, migration and invasion while increased apoptosis of cisplatin-resistant glioma cells and sensitized the cells to cisplatin-induced cell growth arrest and apoptosis. Furthermore, miR‑873 was downregulated while Bcl-2 was upregulated in the tissues of twelve high-grade glioma patients compared to seven normal brain tissues, and the miR‑873 level was negatively correlated with the Bcl-2 protein level. A luciferase reporter assay further confirmed that Bcl-2 was a direct target of miR‑873, and miR‑873 decreased the level of the Bcl-2 protein in cisplatin-resistant glioma cells. Notably, re-expression of Bcl-2 attenuated the function of miR‑873 in cisplatin-resistant glioma cells and the sensitivity of the cells to cisplatin. Taken together, these data suggest that miR‑873 might be a potential marker for cisplatin resistance and a promising sensitizer in cisplatin treatment.
School of Basic Medical Sciences, Wuhan University, Wuhan 430071, P.R. China.
Xiong
X
Chen
School of Basic Medical Sciences, Wuhan University, Wuhan 430071, P.R. China.
Yingying
Y
Zhang
School of Basic Medical Sciences, Wuhan University, Wuhan 430071, P.R. China.
Yingying
Y
Shi
Department of Neurosurgery, Wuhan University Renmin Hospital, Wuhan 430071, P.R. China.
Haiwei
H
Lian
School of Basic Medical Sciences, Wuhan University, Wuhan 430071, P.R. China.
Huilin
H
Tu
School of Basic Medical Sciences, Wuhan University, Wuhan 430071, P.R. China.
Song
S
Han
School of Basic Medical Sciences, Wuhan University, Wuhan 430071, P.R. China.
Biwen
B
Peng
School of Basic Medical Sciences, Wuhan University, Wuhan 430071, P.R. China.
Wanhong
W
Liu
School of Basic Medical Sciences, Wuhan University, Wuhan 430071, P.R. China.
Xiaohua
X
He
D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs; D009361:Neoplasm Invasiveness / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; C000598459:MIRN873 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D002945:Cisplatin