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, Zhi John Lu
Author Information
  1. 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, Beijing 100084, China.
  2. Lei Chen: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
  3. Jin Gu: Bioinformatics Division, TNLIST and Department of Automation, Tsinghua University, Beijing 100084, China. ORCID
  4. Hanshuo Zhang: Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.
  5. 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, Beijing 100084, China.
  6. Qiuyu Lian: Bioinformatics Division, TNLIST and Department of Automation, Tsinghua University, Beijing 100084, China.
  7. Guishuai Lv: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
  8. 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, Beijing 100084, China.
  9. 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, Beijing 100084, China.
  10. 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, Beijing 100084, China.
  11. Dongfang Wang: Bioinformatics Division, TNLIST and Department of Automation, Tsinghua University, Beijing 100084, China.
  12. 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, Beijing 100084, China.
  13. Jing Tang: Department of Neurosurgery, Wuhan General Hospital of Guangzhou Command, Wuhan Hubei 430070, China.
  14. Guijuan Luo: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
  15. 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, Beijing 100084, China.
  16. 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, Beijing 100084, China.
  17. 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, Beijing 100084, China.
  18. 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, Beijing 100084, China.
  19. Mingzhou Guo: Department of Gastroenterology &Hepatology, Chinese PLA General Hospital, #28 Fuxing Road, Beijing 100853, China.
  20. 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, Beijing 100084, China.
  21. Jianzhong Xi: Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.
  22. Hongyang Wang: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
  23. 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, Beijing 100084, China.
  24. 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, Beijing 100084, China.

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.

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MeSH Term

Biomarkers, Tumor
Carcinoma, Hepatocellular
Cell Line, Tumor
Cohort Studies
DNA Copy Number Variations
DNA Methylation
Databases, Genetic
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Hep G2 Cells
Humans
Kaplan-Meier Estimate
Liver Neoplasms
RNA Interference
RNA, Long Noncoding

Chemicals

Biomarkers, Tumor
RNA, Long Noncoding

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