A comprehensive genome-wide analysis of long noncoding RNA expression profile in hepatocellular carcinoma

Cancer Med. 2017 Dec;6(12):2932-2941. doi: 10.1002/cam4.1180. Epub 2017 Oct 18.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, especially in East Asia and China. Long noncoding RNAs (lncRNAs) are emerging as critical regulators that may be involved in the development and progression of cancers in humans. However, the contributions of lncRNAs to HCC development, metastasis, and recurrence remain largely unknown. In this study, we comprehensively investigated lncRNA expression profile in HCC and normal tissues using TCGA RNA sequencing data, one RNA sequencing dataset, and two microarray datasets from GEO. By analyzing these four datasets, we identified hundreds of expression-dysregulated lncRNAs in HCC tissues compared with normal tissues. Genomic copy number variation analysis showed that many of those lncRNAs disorder are related to the copy number amplification or deletion. Moreover, several lncRNAs expression levels are associated with HCC patients' overall and recurrence-free survival, such as RP1-228H13.5, TMCC1-AS1, LINC00205, and RP11-307C12.11. Furthermore, we identified two lncRNAs termed PVT1 and SNHG7 that may be involved in HCC cells metastasis by comparing lncRNAs expression profiles between early recurrence HCC tissues with metastasis and late recurrence HCC tissues without metastasis. Finally, loss-of-function assays confirmed that knockdown of SNHG7 and PVT1 impaired HCC cells invasion. Taken together, these findings may provide a valuable resource for further identification of novel biomarkers and therapeutic targets for HCC patients.

Keywords: HCC; Biomarker; SNHG7; lncRNA; metastasis.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy
  • Cell Line, Tumor
  • Cell Movement
  • Computational Biology
  • DNA Copy Number Variations
  • Databases, Genetic
  • Disease Progression
  • Disease-Free Survival
  • Gene Amplification
  • Gene Deletion
  • Gene Dosage
  • Gene Expression Profiling / methods*
  • Genome-Wide Association Study
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local
  • Oligonucleotide Array Sequence Analysis
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Neoplasm / genetics*
  • RNA, Neoplasm / metabolism
  • Time Factors
  • Transcriptome*
  • Transfection
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • PVT1 long-non-coding RNA, human
  • RNA, Long Noncoding
  • RNA, Neoplasm