Recurrently deregulated lncRNAs in hepatocellular carcinoma

Yang Yang, Lei Chen, Jin Gu, Hanshuo Zhang, Jiapei Yuan, Qiuyu Lian, Guishuai Lv, Siqi Wang, Yang Wu, Yu-Cheng T. Yang, Dongfang Wang, Yang Liu, Jing Tang, Guijuan Luo, Yang Li, Long Hu, Xinbao Sun, Dong Wang, Mingzhou Guo, Qiaoran Xi, Jianzhong Xi, Hongyang Wang (), Michael Q. Zhang () and Zhi John Lu ()
Additional contact information
Yang Yang: 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
Lei Chen: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University
Jin Gu: Tsinghua University
Hanshuo Zhang: College of Engineering, Peking University
Jiapei Yuan: 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
Qiuyu Lian: Tsinghua University
Guishuai Lv: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University
Siqi Wang: 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
Yang Wu: 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
Yu-Cheng T. Yang: 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
Dongfang Wang: Tsinghua University
Yang Liu: 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
Jing Tang: Wuhan General Hospital of Guangzhou Command
Guijuan Luo: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University
Yang Li: 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
Long Hu: 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
Xinbao Sun: 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
Dong Wang: 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
Mingzhou Guo: Chinese PLA General Hospital
Qiaoran Xi: 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
Jianzhong Xi: College of Engineering, Peking University
Hongyang Wang: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University
Michael Q. Zhang: 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
Zhi John Lu: 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

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14421

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