title: Amplification of Long Noncoding RNA ZFAS1 Promotes Metastasis in Hepatocellular Carcinoma.
abstract: Despite progress in the diagnostics and treatment of hepatocellular carcinoma (HCC), its prognosis remains poor. In this study, we globally assessed long noncoding RNAs (lncRNA) for contributions to HCC using publicly available microarray data, in vitro and in vivo assays. Here, we report that ZFAS1, encoding a lncRNA that is frequently amplified in HCC, is associated with intrahepatic and extrahepatic metastasis and poor prognosis of HCC. ZFAS1 functions as an oncogene in HCC progression by binding miR-150 and abrogating its tumor-suppressive function in this setting. miR-150 repressed HCC cell invasion by inhibiting ZEB1 and the matrix metalloproteinases MMP14 and MMP16. Conversely, ZFAS1 activated ZEB1, MMP14, and MMP16 expression, inhibiting these effects of miR-150. Our results establish a function for ZFAS1 in metastatic progression and suggest its candidacy as a new prognostic biomarker and target for clinical management of HCC.
authors.affiliation: Department of Hepato-Bilio-Pancreatic Surgery, Shanghai Institute of Digestive Surgery, Rui Jin Hospital affiliated with Shanghai Jiaotong University, Shanghai, China.
authors.forename: Tao
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, China.
authors.forename: Junjie
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, China.
authors.forename: Chuan
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, China.
authors.forename: Dongfeng
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, China.
authors.forename: Yuan
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, China.
authors.forename: Zhichong
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, China.
authors.forename: Xiaxing
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, China.
authors.forename: Hao
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, China.
authors.forename: Baiyong
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, China.
authors.forename: Chenghong
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, China.
authors.forename: Hongwei
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, China.
authors.forename: Qian
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, China. zhuzhecheng@126.com.
authors.forename: Zhecheng
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D053511:Matrix Metalloproteinase 14 / Q000235:genetics; D053513:Matrix Metalloproteinase 16 / Q000235:genetics; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D018398:Homeodomain Proteins; D053511:Matrix Metalloproteinase 14; D053513:Matrix Metalloproteinase 16; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D014157:Transcription Factors; D000071799:Zinc Finger E-box-Binding Homeobox 1; C533097:MIR150, human; C507102:MMP16 protein, human; C486307:ZEB1 protein, human; C000611949:ZFAS1 long non-coding RNA, human; C507086:MMP14 protein, human