title: HNRNPAB induces epithelial-mesenchymal transition and promotes metastasis of hepatocellular carcinoma by transcriptionally activating SNAIL.
abstract: Expression of heterogeneous nuclear ribonucleoprotein AB (HNRNPAB) has been reported to be dysregulated in tumors, but its specific contributions to tumor formation and progression are not fully understood. Here, we demonstrate that HNRNPAB is overexpressed in highly metastatic cells and tumor tissues from patients with hepatocellular carcinoma (HCC) with recurrence. We found that HNRNPAB overexpression promoted epithelial-mesenchymal transition (EMT) in a manner associated with HCC metastasis in vitro and in vivo. RNA interference-mediated silencing of the EMT factor SNAIL attenuated HNRNPAB-enhanced cell invasion in vitro and lung metastasis in vivo. Mechanistically, HNRNPAB acted to transactivate SNAIL1 transcription, which in turn inhibited transcription of the pivotal SNAIL target gene E-cadherin. Overexpression of HNRNPAB in HCC samples correlated with higher SNAIL levels, shorter overall survival, and higher tumor recurrence. HNRNPAB overexpression, alone or in combination with SNAIL, was found to be a significant independent risk factor for recurrence and survival after curative resection. In conclusion, our findings define HNRNPAB as an activator of EMT and metastasis in HCC that predicts poor clinical outcomes.
authors.affiliation: Authors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, ChinaAuthors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Zheng-Jun
authors.initials: ZJ
authors.lastname: Zhou
authors.affiliation: Authors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, ChinaAuthors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Authors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, ChinaAuthors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Shao-Lai
authors.initials: SL
authors.lastname: Zhou
authors.affiliation: Authors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, ChinaAuthors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Hu
authors.affiliation: Authors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, ChinaAuthors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Authors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, ChinaAuthors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Zhao
authors.affiliation: Authors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, ChinaAuthors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Shi
authors.affiliation: Authors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, ChinaAuthors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Authors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, ChinaAuthors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Wu
authors.affiliation: Authors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, ChinaAuthors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Shuang-Jian
authors.initials: SJ
authors.lastname: Qiu
authors.affiliation: Authors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, ChinaAuthors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, ChinaAuthors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Authors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, ChinaAuthors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, ChinaAuthors' Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; and Institute of Biomedical Sciences, Fudan University, Shanghai, China fan.jia@zs-hospital.sh.cn jiafan99@yahoo.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015331:Cohort Studies; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D056945:Hep G2 Cells; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C103749:HNRNPAB protein, human; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; C000604407:SNAI1 protein, human; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors