title: Recurrently deregulated lncRNAs in hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) cells often invade the portal venous system and subsequently develop into portal vein tumour thrombosis (PVTT). Long noncoding RNAs (lncRNAs) have been associated with HCC, but a comprehensive analysis of their specific association with HCC metastasis has not been conducted. Here, by analysing 60 clinical samples' RNA-seq data from 20 HCC patients, we have identified and characterized 8,603 candidate lncRNAs. The expression patterns of 917 recurrently deregulated lncRNAs are correlated with clinical data in a TCGA cohort and published liver cancer data. Matched array data from the 60 samples show that copy number variations (CNVs) and alterations in DNA methylation contribute to the observed recurrent deregulation of 235 lncRNAs. Many recurrently deregulated lncRNAs are enriched in co-expressed clusters of genes related to cell adhesion, immune response and metabolic processes. Candidate lncRNAs related to metastasis, such as HAND2-AS1, were further validated using RNAi-based loss-of-function assays. Thus, we provide a valuable resource of functional lncRNAs and biomarkers associated with HCC tumorigenesis and metastasis.
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Center for Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.|National Center for Liver Cancer, Shanghai 201805, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Bioinformatics Division, TNLIST and Department of Automation, Tsinghua University, Beijing 100084, China.
authors.forename: Jin
authors.identifier: 0000-0003-3968-8036
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.
authors.forename: Hanshuo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Center for Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Jiapei
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Bioinformatics Division, TNLIST and Department of Automation, Tsinghua University, Beijing 100084, China.
authors.forename: Qiuyu
authors.initials: Q
authors.lastname: Lian
authors.affiliation: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
authors.forename: Guishuai
authors.initials: G
authors.lastname: Lv
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Center for Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Center for Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Center for Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yu-Cheng T
authors.initials: YT
authors.lastname: Yang
authors.affiliation: Bioinformatics Division, TNLIST and Department of Automation, Tsinghua University, Beijing 100084, China.
authors.forename: Dongfang
authors.initials: D
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Center for Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Wuhan General Hospital of Guangzhou Command, Wuhan Hubei 430070, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tang
authors.affiliation: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
authors.forename: Guijuan
authors.initials: G
authors.lastname: Luo
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Center for Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Center for Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Long
authors.initials: L
authors.lastname: Hu
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Center for Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xinbao
authors.initials: X
authors.lastname: Sun
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Center for Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology &Hepatology, Chinese PLA General Hospital, #28 Fuxing Road, Beijing 100853, China.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Guo
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Center for Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Qiaoran
authors.initials: Q
authors.lastname: Xi
authors.affiliation: Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Xi
authors.affiliation: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.|National Center for Liver Cancer, Shanghai 201805, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Center for Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.|Bioinformatics Division, TNLIST and Department of Automation, Tsinghua University, Beijing 100084, China.|Department of Biological Sciences, Center for Systems Biology, The University of Texas at Dallas, 800 West Campbell Road, RL11 Richardson, Texas 75080-3021, USA.
authors.forename: Michael Q
authors.initials: MQ
authors.lastname: Zhang
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Center for Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zhi John
authors.initials: ZJ
authors.lastname: Lu
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D056945:Hep G2 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding