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Elevated miR-101 Reduces Resistance of Cervical Carcinoma CaSki Cells to Cisplatin by Inhibiting the Expression of mTOR miR-101 and Cervical Cancer Cell Cisplatin Resistance

Journal 2018 · IF 0.781 · 8(3): 426-432 · 发表于 2018 年 3 月 1 日
作者: Hu Jinghui,Wang Li,Shen Heping,Huang Yujie,Zhao Wei
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摘要

The elevated expression of mammalian target of rapamycin (mTOR) is associated with the occurrence, progression, and drug resistance of various tumors. Studies have shown overexpression of mTOR and reduced expression of miR-101 in cervical cancer tissues. Bioinformatic analysis has revealed that a targeting binding site exists between miR-101 and the 3'-UTR of mTOR mRNA. In this study we determined whether miR-101 played a role in regulating mTOR expression and influencing the proliferation, apoptosis, and drug resistance to cisplatin (DDP) of CC cells. The regulatory relationship between miR-101 and mTOR was validated by dual-luciferase reporter gene assay. The DDP resistance cell line, CaSki/DDP, was established, and the expressions of miR-101, mTOR, p-mTOR, and p-4EBP1 in the CaSki/DDP cell line and parental CaSki cells. The effect of DDP treatment on the proliferation and apoptosis of the two cell lines were detected by flow cytometry. CaSki/DDP cells were divided into the following four transfection groups: miR-NC group; miR-101 mimic group; si-NC group; and si-mTOR group. The expression of miR-101, MTOR, p-mTOR, and p-4EBP1 was determined, and the effect of DDP treatment on the proliferation and apoptosis of the two cell lines we detected by flow cytometry. There was a targeted regulatory relationship between miR-101 and mTOR. The expression and apoptosis rate of miR-101 in CaSki/DDP cells were significantly lower than CaSki cells, while the expression and proliferation of mTOR, p-mTOR, and p-4EBP1 in CaSki/DDP cells were significantly higher than CaSki cells. The transfection of miR-101 mimic or si-mTOR significantly reduced the expression of mTOR, p-mTOR, and p-4EBP1 in CaSki/DDP cells and weakened the cell proliferation ability. DDP treatment significantly increased the apoptosis rate. The decreased expression of miR-101 is associated with CaSki/DD cell resistance to DDP. Overexpression of miR-101 can reduce the resistance of cervical cancer CaSki/DDP cells to DDP by targeted inhibition of the expression of mTOR.