MicroRNA-21 regulates the migration and invasion of a stem-like population in hepatocellular carcinoma

被引:105
|
作者
Zhou, Liang [1 ]
Yang, Zhao-Xu [2 ]
Song, Wen-Jie [2 ]
Li, Qing-Jun [2 ]
Yang, Fan [2 ]
Wang, De-Sheng [2 ]
Zhang, Ning [2 ]
Dou, Ke-Feng [2 ]
机构
[1] 155 Cent Hosp PLA, Dept Gen Surg, Kaifeng 471000, Henan, Peoples R China
[2] Fourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian 710032, Shannxi, Peoples R China
基金
中国国家自然科学基金;
关键词
hepatocellular carcinoma; microRNA-21; cancer stem cell; side population; migration; invasion; TUMOR-SUPPRESSOR PDCD4; CANCER CELL-LINES; SIDE POPULATION; EXPRESSION PROFILES; HUMAN BRAIN; PTEN; BREAST; IDENTIFICATION; METASTASIS; INHIBITOR;
D O I
10.3892/ijo.2013.1965
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Due to invasion and intrahepatic metastasis, the prognosis for patients with hepatocellular carcinoma (HCC) is poor. However, the mechanisms underlying these processes of HCC remain unclear. Cancer stem cells may be involved in early systemic dissemination and metastasis formation and side population (SP) cells isolated from diverse cancer cells possess stem cell-like properties. However, the mechanisms involved in migration and invasion of cancer stem cells are not well understood. In this study, we identified and isolated populations of SP cells from HCC cell lines using flow cytometry. SP cells showed higher levels of migration and invasion capability. Higher expression of miR-21 was observed in SP cells. Silencing of miR-21 led to a reduction in the migration and invasion of these cells and overexpression of miR-21 can increase in cell migration and invasion. Overexpression of miR-21 did not cause degradation of PTEN or RECK or PDCD4 mRNA but drastically inhibited its protein expression. Consistent with these results, silencing miR-21 increased the levels of PTEN, RECK and PDCD4 protein, respectively. The role of silencing miR-21 was partially attenuated by silencing of PTEN or RECK or PDCD4 mRNA. The results of this study revealed the aberrant expression of miR-21 in SP cells and showed that miR-21 regulates the expression of multiple target proteins that are associated with tumor dissemination. MiR-21 is a pro-metastatic miRNA in SP cells and raises the possibility that therapy of HCC may be improved by pharmaceutical strategies directed towards miR-21.
引用
收藏
页码:661 / 669
页数:9
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