1. MicroRNA-122 sensitizes HCC cancer cells to adriamycin and vincristine through modulating expression of MDR and inducing cell cycle arrest
- Author
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Xu, Yanmin, Xia, Feng, Ma, Leina, Shan, Juanjuan, Shen, Junjie, Yang, Zhi, Liu, Jia, Cui, Youhong, Bian, Xiuwu, Bie, Ping, and Qian, Cheng
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LIVER cancer , *RNA , *DOXORUBICIN , *MULTIDRUG resistance , *CELL cycle , *CANCER chemotherapy , *VINCRISTINE - Abstract
Abstract: Hepatocellular carcinoma (HCC) is a hypervascular cancer characterized by rapid progression as well as resistance to conventional chemotherapy. It has been shown that microRNAs play critical roles in pathogenesis of HCC. MicroRNA-122 (miR-122) is a liver-specific microRNA and is frequently downregulated in HCC. In the present study, we investigated whether restoration of miR-122 in HCC cells could render cells sensitive to chemotherapeutic agents adriamycin (ADM) or vincristine (VCR). Our data showed that overexpression of miR-122 in HCC cells induced by adenovirus expressing miR-122 could render cell sensitive to ADM or VCR. Analysis of cell cycle distribution showed that the anti-proliferative effect of miR-122 is associated with increase of cell number in the G2/M phase. Moreover, treatment with Ad-miR122 and ADM or VCR resulted in high accumulation of HCC cells in G2/M phase. We further demonstrated that overexpression of miR-122 could modulate the sensitivity of the HCC cells to chemotherapeutic drugs through downregulating MDR related genes MDR-1, GST-π, and MRP, antiapoptotic gene Bcl-w and cell cycle related gene cyclin B1. Taken together, our findings demonstrated that combination of Ad-miR122 with chemotherapeutic agents inhibited HCC cell growth by inducing G2/M arrest and that this arrest is associated, at least in part, with reduced expression of MDR related genes and Cyclin B1. [Copyright &y& Elsevier]
- Published
- 2011
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