title: Upregulation of long noncoding RNA ZEB1-AS1 promotes tumor metastasis and predicts poor prognosis in hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Despite progress in diagnostics and treatment of HCC, its prognosis remains poor. Emerging studies showed that long noncoding RNAs (lncRNAs) have crucial regulatory roles in cancer biology. In the current study, differentially expressed lncRNAs between HCC and paired non-tumor tissues were identified using microarrays. The effects of a specific differentially expressed lncRNA (termed ZEB1-AS1) on tumor progression were investigated in vitro and in vivo. We found that ZEB1-AS1 is frequently upregulated in HCC samples, especially in metastatic tumor tissues. DNA methylation analysis shows a tumor-specific ZEB1-AS1 promoter hypomethylation. Aberrant methylation is tightly correlated with overexpression of ZEB1-AS1 in HCC. Patients with ZEB1-AS1 hypomethylation or with high ZEB1-AS1 expression have poor recurrence-free survival. Functionally, ZEB1-AS1 promotes tumor growth and metastasis, acts as an oncogene in HCC. The ZEB1-AS1 gene is located in physical contiguity with ZEB1 and positively regulates the ZEB1 expression. ZEB1 inhibition partially abrogates ZEB1-AS1-induced epithelial to mesenchymal transition (EMT) and cancer metastasis. Our results provide novel insights into the function of lncRNA-driven hepatocarcinogenesis, highlight the important role of ZEB1-AS1 and ZEB1 in HCC progression, and indicate that ZEB1-AS1 may be served as a valuable prognostic biomarker for HCC.
authors.affiliation: Department of Hepato-Bilio-Pancreatic Surgery, Shanghai Institute of Digestive Surgery, Rui Jin Hospital affiliated with Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: T
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Hepato-Bilio-Pancreatic Surgery, Shanghai Institute of Digestive Surgery, Rui Jin Hospital affiliated with Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Hepato-Bilio-Pancreatic Surgery, Shanghai Institute of Digestive Surgery, Rui Jin Hospital affiliated with Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: C
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Hepato-Bilio-Pancreatic Surgery, Shanghai Institute of Digestive Surgery, Rui Jin Hospital affiliated with Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: D
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Department of Hepato-Bilio-Pancreatic Surgery, Shanghai Institute of Digestive Surgery, Rui Jin Hospital affiliated with Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Hepato-Bilio-Pancreatic Surgery, Shanghai Institute of Digestive Surgery, Rui Jin Hospital affiliated with Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Hepato-Bilio-Pancreatic Surgery, Shanghai Institute of Digestive Surgery, Rui Jin Hospital affiliated with Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Hepato-Bilio-Pancreatic Surgery, Shanghai Institute of Digestive Surgery, Rui Jin Hospital affiliated with Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Hepato-Bilio-Pancreatic Surgery, Shanghai Institute of Digestive Surgery, Rui Jin Hospital affiliated with Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: B
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Hepato-Bilio-Pancreatic Surgery, Shanghai Institute of Digestive Surgery, Rui Jin Hospital affiliated with Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: C
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Hepato-Bilio-Pancreatic Surgery, Shanghai Institute of Digestive Surgery, Rui Jin Hospital affiliated with Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Hepato-Bilio-Pancreatic Surgery, Shanghai Institute of Digestive Surgery, Rui Jin Hospital affiliated with Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhan
authors.affiliation: Department of Hepato-Bilio-Pancreatic Surgery, Shanghai Institute of Digestive Surgery, Rui Jin Hospital affiliated with Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D018398:Homeodomain Proteins; D062085:RNA, Long Noncoding; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1