title: Zinc finger protein ZBTB20 is an independent prognostic marker and promotes tumor growth of human hepatocellular carcinoma by repressing FoxO1.
abstract: Zinc finger and BTB domain-containing 20 (ZBTB20) is a new BTB/POZ-domain gene and a member of the POK family of transcriptional repressors. Notably, the role of ZBTB20 and its underlying mechanisms involved in hepatocarcinogenesis are poorly investigated. In this study, the expression of ZBTB20 was significantly overexpressed in hepatocellular carcinoma (HCC) tissues. The positive expression of ZBTB20 was associated with large tumor size, high Edmondson-Steiner grading and advanced tumor-node-metastasis (TNM) tumor stage. Additionally, HCC patients with positive expression of ZBTB20 had a poorer 5-year survival. Multivariate analyses revealed that ZBTB20 overexpression was an independent prognostic factor for HCC. Gain- and loss-of-function experiments demonstrated that ZBTB20 promoted HCC cell viability, proliferation, tumorigenicity, and cell cycle progression. Mechanistically, Cyclin D1 and Cyclin E were increased, while p21 and p27 were decreased by ZBTB20 in HCC cells. FoxO1 was inversely correlated with ZBTB20 protein expression in the same cohort of HCC specimens. We further revealed that FoxO1 was transcriptionally repressed by ZBTB20 in HCC. Moreover, restoration of FoxO1 expression partially abrogated ZBTB20-induced HCC cell proliferation and growth entry in vitro and in vivo. Collectively, these results indicate that ZBTB20 may serve as a prognostic marker and promotes tumor growth of HCC via transcriptionally repressing FoxO1.
authors.affiliation: Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Heping
authors.initials: H
authors.lastname: Kan
authors.affiliation: Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Infectious Disease, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Dingli
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jianjia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Miaojiang
authors.initials: M
authors.lastname: Shu
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D000071161:Forkhead Box Protein O1 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D016335:Zinc Fingers
chemical_list: D014408:Biomarkers, Tumor; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C427486:ZBTB20 protein, human
keywords: FoxO1; ZBTB20; cell cycle; hepatocellular carcinoma; proliferation