VCP/p97, Down-Regulated by microRNA-129-5p, Could Regulate the Progression of Hepatocellular Carcinoma
Open Access
- 20 April 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (4), e35800
- https://doi.org/10.1371/journal.pone.0035800
Abstract
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 IκBα 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.Keywords
This publication has 34 references indexed in Scilit:
- Lupeol targets liver tumor-initiating cells through phosphatase and tensin homolog modulationHepatology, 2010
- Epigenetic Repression of microRNA-129-2 Leads to Overexpression of SOX4 Oncogene in Endometrial CancerCancer Research, 2009
- Effects of MicroRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinomaHepatology, 2009
- MicroRNA Expression, Survival, and Response to Interferon in Liver CancerNew England Journal of Medicine, 2009
- MicroRNA-101, Down-regulated in Hepatocellular Carcinoma, Promotes Apoptosis and Suppresses TumorigenicityCancer Research, 2009
- MicroRNA-101 regulates expression of the v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) oncogene in human hepatocellular carcinomaHepatology, 2008
- MicroRNA-21 Regulates Expression of the PTEN Tumor Suppressor Gene in Human Hepatocellular CancerGastroenterology, 2007
- Pre-B-Cell Leukemia Transcription Factor 1 Regulates Expression of Valosin-Containing Protein, a Gene Involved in Cancer GrowthThe American Journal of Pathology, 2007
- MicroRNAs: small RNAs with a big role in gene regulationNature Reviews Genetics, 2004
- Apoptosis in cancer—implications for therapySeminars in Oncology, 2004