title: HBP21, a chaperone of heat shock protein 70, functions as a tumor suppressor in hepatocellular carcinoma.
abstract: Inactivation of tumor suppressor genes, caused by genetic and epigenetic alterations, is one of the key issues in the development and progression of cancer. To identify and characterize cancer related genes in hepatocellular carcinoma (HCC) pathogenesis, transcriptome sequencing has been applied to compare expression profiles between tumor and non-tumor tissues. Among the down-regulated genes, heat shock binding protein 21 (HBP21) was selected for further study. In this study, down-regulation of HBP21 was frequently detected in primary HCCs (87/120, 72.5%), which was significantly associated with advanced clinical stage (P = 0.049), poor differentiation (P = 0.018) and poor prognosis (P = 0.026). Further study found that down-regulation of HBP21 in HCC was mainly caused by allele loss and promoter methylation. Functional study found that HBP21 could inhibit tumor cell growth rate, foci formation and colony formation in soft agar, and tumor formation in nude mice when it was transfected into HCC cells. Molecular study found that HBP21 could promote cell apoptosis, especially under adverse conditions such as heat and chemotherapeutic agent treatment. As a chaperone of heat shock protein 70 (HSP70), HBP21 could inhibit interaction between HSP70 and Bax, increased Bax protein translocation from cytoplasm to mitochondria, and subsequently increased the release of cytochrome c into cytoplasm, and finally induced apoptosis. Clinically, HBP21 could be used as a prognostic biomarker for HCC outcome prediction and might be also as a novel therapeutic agent in HCC treatment.
authors.affiliation: Department of Clinical Oncology, State Key Laboratory for Liver Research, Center for Cancer Research, The University of Hong Kong, Hong Kong, China.
authors.forename: Lingxi
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Clinical Oncology.
authors.forename: Dora Lai-Wan
authors.initials: DL
authors.lastname: Kwong
authors.affiliation: Department of Clinical Oncology, State Key Laboratory for Liver Research, Center for Cancer Research, The University of Hong Kong, Hong Kong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Clinical Oncology, State Key Laboratory for Liver Research, Center for Cancer Research, The University of Hong Kong, Hong Kong, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China and.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China and.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Shenzhen Key Laboratory of translational Medicine of Tumor and Cancer Research Centre, School of Medicine, Shenzhen University, Shenzhen 518060, China.
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Clinical Oncology, State Key Laboratory for Liver Research, Center for Cancer Research, The University of Hong Kong, Hong Kong, China, State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China and xyguan@hku.hk.
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: C494826:BAX protein, human; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; C539084:TTC36 protein, human; D051028:bcl-2-Associated X Protein