MicroRNA-195 reverses the resistance to temozolomide through targeting cyclin E1 in glioma cells

作者：Wang, Hongqin^*; Ren, Shuxian; Xu, Yongming; Miao, Wang; Huang, Xintao; Qu, Zhizhao; Li, Jinhu; Liu, Xiaodong; Kong, Pengzhou

来源：Anti-Cancer Drugs, 2019, 30(1): 81-88.

DOI：10.1097/CAD.0000000000000700

• chemoresistance
• cyclin E1
• glioblastoma
• microRNA-195
• temozolomide

Glioma is the most common malignant tumor of the central nervous system with poor survival. Temozolomide (TMZ) is the first-line chemotherapy drug for initial and recurrent glioma treatment with a relatively good efficacy, which exerts its antitumor effects mainly through cell death induced by DNA double-strand breaks in the G1 and S phases. However, endogenous or acquired resistance to TMZ limits glioma patients' clinical outcome and is also an important cause of glioma replase. MicroRNA-195 (miR-195) plays an important role in the regulation of G1-phase/S-phase transition, DNA damage repair, and apoptosis of tumor cells. We found that miR-195 expression was significantly decreased in TMZ-resistant glioma cells induced with TMZ and correlated to the resistance index negatively. Also, the exogenous expression of miR-195 reversed TMZ resistance and induced the apoptosis of TMZ-resistant glioblastoma cells. Further bioinformatics analysis showed cyclin E1 (CCNE1) was a potential target gene of miR-195. Knockdown of CCNE1 partially reversed the effect of decreased miR-195 on TMZ resistance. The data from The Cancer Genome Atlas - Cancer Genome further suggested that hsa-miR-195 could negatively regulate the expression of CCNE1 in glioma. In conclusion, miR-195 reverses the resistance to TMZ by targeting CCNE1 in glioma cells and it could act as a potential target for treatment in glioma with TMZ resistance.

• 出版日期2019-1
• 单位山西医科大学