Invasion and metastasis-related long noncoding RNA expression profiles in hepatocellular carcinoma

Tumour Biol. 2015 Sep;36(10):7409-22. doi: 10.1007/s13277-015-3408-0. Epub 2015 Apr 22.

Abstract

Recurrence, invasion, and metastasis are the major reasons of the low 5-year survival of hepatocellular carcinoma. However, the mechanisms of recurrence, invasion, and metastasis are still poll understood. Long noncoding RNAs (LncRNAs, >200 nt) have been demonstrated to play important roles in both tumor suppressive and oncogenic signaling pathways. Here, we employed the LncRNAs microarray technology to study the LncRNAs expression profiles at genome-wide in hepatocellular carcinoma (HCC) tissue samples with early recurrence (less than 1 year, with invasion and metastasis out of liver) and late recurrence (longer than 2 years, without invasion and metastasis out of liver), which had different recurrent/metastatic potentials, by using normal liver tissue as control to screen the dysregulated LncRNAs which are potentially involved in the recurrence, invasion, and metastasis process of HCC. Overall, 1170 LncRNAs were identified to differentially expressed between the early and late recurrence samples. These differentially expressed LncRNAs were further characterized by integrating examination of genomic context, co-expression network analysis, and gene ontology (GO) enrichment of their associated protein-coding genes. Furthermore, 15 LncRNAs selected randomly from top 50 differentially expressed LncRNAs were validated by quantitative PCR (qPCR) in cell lines MHCC97H and MHCC97L, which have exactly the same genetic background but with different invasion potentials. Meanwhile, the prognostic potential of three verified LncRNAs at cell line level was further validated in 59 HCC samples. Therefore, our results demonstrated that the aberrant expression of LncRNAs might be responsible for the HCC invasion and metastasis and provide fundamental information for further study the LncRNAs involved molecular mechanisms of the invasion and metastasis of HCC.

Keywords: Expression profiles; Hepatocellular carcinoma; Invasion; Long noncoding RNA; Metastasis; Recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / secondary
  • Follow-Up Studies
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Gene Ontology
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Lymphatic Metastasis
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics*
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction

Substances

  • RNA, Long Noncoding
  • RNA, Messenger