VCP/p97, Down-Regulated by microRNA-129-5p, Could Regulate the Progression of Hepatocellular Carcinoma

被引:78
|
作者
Liu, Yu [1 ]
Hei, Yan [2 ]
Shu, Qingming [2 ]
Dong, Jie [1 ]
Gao, Yaping [1 ]
Fu, Hanjiang [3 ]
Zheng, Xiaofei [3 ]
Yang, Guang [1 ]
机构
[1] Beijing Inst Basic Med Sci, Beijing, Peoples R China
[2] Peoples Armed Police Corps Gen Hosp, Beijing, Peoples R China
[3] Beijing Inst Radiat Med, Beijing, Peoples R China
来源
PLOS ONE | 2012年 / 7卷 / 04期
关键词
VALOSIN-CONTAINING-PROTEIN; NF-KAPPA-B; ELEVATED EXPRESSION; INDUCED APOPTOSIS; CANCER; P97; PROGNOSIS; ATPASE; CELLS; LIVER;
D O I
10.1371/journal.pone.0035800
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Valosin containing protein (VCP)/p97 plays various important roles in cells. Moreover, elevated expression of VCP in hepatocellular carcinoma (HCC) is correlated with increased incidence of recurrence. But the role of VCP in HCC progression in vitro and in vivo is unclear. And there are few reports about the regulation mechanism on the expression of VCP in HCC. In this study, it was identified that the level of VCP was frequently increased in human HCC tissues. In addition, down-regulation of VCP with siRNAs could dramatically suppress the genesis and progression of tumor in vivo. It was found that miR-129-5p directly inhibited the expression of VCP in several HCC cell lines. Meanwhile, the level of VCP in HCC tissues was negatively associated with the level of miR-129-5p. Our further investigation showed that the enhanced expression of miR-129-5p also suppressed tumor growth in vivo. Moreover, it was revealed that miR-129-5p could inhibit the degradation of I kappa B alpha and increase the apoptosis and reduce the migration of HCC cells by suppressing the expression of VCP. Our results revealed that the expression of VCP was directly regulated by miR-129-5p and this regulation played an important role in the progression of HCC.
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页数:8
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