title: Vigilin is overexpressed in hepatocellular carcinoma and is required for HCC cell proliferation and tumor growth.
abstract: Vigilin contains multiple KH domains and is an evolutionarily conserved RNA-binding protein from yeast to the human. Its reported roles in human carcinogenesis are controversial in different types of human cancers. To obtain the specific expression profiles of vigilin in human hepatocellular carcinomas (HCCs), we examined vigilin protein levels in normal human liver, liver cirrhosis, adjacent non-tumor liver and HCC tumor tissues as well as in several HCC cell lines. We discovered that vigilin expression increased progressively from the liver cirrhosis tissue to adjacent non-tumor liver tissue and then to HCC tumor cells. Vigilin protein was also overexpressed in all three HCC cell lines examined, HepG2, BEL7402 and SMMC7721, when compared with the vigilin expression level in the L-02 human embryonic hepatocyte cell line. We further investigated the impact of vigilin knockdown on HCC cell proliferation, survival, motility, tumor growth and sensitivity to chemotherapy. We found that knockdown of vigilin in the BEL7402 HCC cells significantly inhibited their proliferation, colony formation and migration, but largely enhanced the cisplatin treatment-induced growth inhibition of these cells in culture. We also found that vigilin knockdown effectively inhibited the growth of BEL7402 cell-derived xenograft tumors in nude mice by decreasing the proliferation and increasing the apoptosis of the BEL7402 HCC cells. Taken together, these results suggest that progressively upregulated vigilin may serve as a molecular risk marker for HCC development, and targeting vigilin may help to inhibit HCC cell growth, survival and migration.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Preclinical and Forensic Medicine, West China Medical Center, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Wen Li
authors.initials: WL
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Preclinical and Forensic Medicine, West China Medical Center, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Preclinical and Forensic Medicine, West China Medical Center, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Wen Qing
authors.initials: WQ
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Preclinical and Forensic Medicine, West China Medical Center, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Preclinical and Forensic Medicine, West China Medical Center, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Wen Yan
authors.initials: WY
authors.lastname: Shen
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Preclinical and Forensic Medicine, West China Medical Center, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Jian Yu
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Institute for Cancer Medicine, Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China.
authors.forename: Jian Ming
authors.initials: JM
authors.lastname: Xu
authors.affiliation: Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Preclinical and Forensic Medicine, West China Medical Center, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Qin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D034622:RNA Interference; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C075197:high density lipoprotein binding protein; D002945:Cisplatin