microRNA-19a-3p promotes tumor metastasis and chemoresistance through the PTEN/Akt pathway in hepatocellular carcinoma

被引:87
作者
Jiang, Xue-Mei [1 ,2 ]
Yu, Xiang-Nan [1 ]
Liu, Tao-Tao [1 ]
Zhu, Hai-Rong [1 ]
Shi, Xuan [1 ]
Bilegsaikhan, Enkhnaran [1 ]
Guo, Hong-Ying [1 ]
Song, Guang-Qi [1 ]
Weng, Shu-Qiang [1 ]
Huang, Xiao-Xi [2 ]
Dong, Ling [1 ]
Janssen, Harry L. A. [3 ,4 ]
Shen, Xi-Zhong [1 ,5 ,6 ]
Zhu, Ji-Min [1 ]
机构
[1] Fudan Univ, Dept Gastroenterol, Zhongshan Hosp, 180 Fenglin Rd, Shanghai 200032, Peoples R China
[2] Cent South Univ, Dept Gastroenterol, Xiangya Sch Med, Affiliated Haikou Hosp, Haikou, Hainan, Peoples R China
[3] Univ Toronto, Div Gastroenterol, Toronto, ON, Canada
[4] Univ Hlth Network, Toronto, ON, Canada
[5] Shanghai Inst Liver Dis, Shanghai, Peoples R China
[6] Fudan Univ, Key Lab Med Mol Virol, Shanghai Med Coll, Shanghai, Peoples R China
关键词
microRNA-19a-3p; Hepatocellular carcinoma; Metastasis; Chemoresistance; EPITHELIAL-MESENCHYMAL TRANSITION; PI3K/AKT PATHWAY; SUPPRESSOR GENE; CANCER CELLS; RESISTANCE; MIR-19A; SORAFENIB; PROGNOSIS; EXPRESSION; CONFERS;
D O I
10.1016/j.biopha.2018.06.097
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
microRNA-19a-3p (miR-19a-3p) has been reported to regulate cell proliferation in hepatocellular carcinoma (HCC), but its role in HCC metastasis remains unknown. In this study, miR-19a-3p was noted to be upregulated in HCC specimens and cell lines. Aberrant expression of miR-19a-3p stimulated HCC cell metastasis, and phosphatase and tensin homolog (PTEN) was shown to be a direct target of miR-19a-3p. miR-19a-3p-mediated HCC metastasis was reversed by restoration of PTEN or could be imitated by silencing of PTEN. Modulation of miR-19a-3p also altered expression of phosphorylated Akt, a downstream mediator of PTEN. Moreover, aberrant expression of miR-19a-3p induced sorafenib resistance by regulating the PTEN/Akt pathway. In conclusion, ectopic expression of miR-19a-3p contributes to HCC metastasis and chemoresistance by modulating PTEN expression and the PTEN-dependent pathways.
引用
收藏
页码:1147 / 1154
页数:8
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