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Transcriptomic Analysis of mRNA-lncRNA-miRNA Interactions in Hepatocellular Carcinoma

Xia Tang1, Delong Feng2, Min Li3

  • 1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.

Scientific Reports
|November 8, 2019
PubMed

Insights

This study reveals a complex network of non-coding RNAs (ncRNAs) in liver cancer. Understanding these microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) interactions offers new insights into hepatocarcinogenesis.

Area of Science:

  • Molecular Biology
  • Genomics
  • Cancer Research

Background:

  • Hepatocellular carcinoma (HCC) pathogenesis involves complex molecular mechanisms.
  • The role of non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in HCC is not fully understood.

Purpose of the Study:

  • To characterize ncRNA expression profiles in HCC.
  • To construct a regulatory messenger RNA (mRNA)-lncRNA-miRNA (MLMI) network in HCC.
  • To elucidate the molecular mechanisms underlying hepatocarcinogenesis.

Main Methods:

  • Transcriptome sequencing (RNA-seq) on HCC patient samples (n=9).
  • Identification and differential expression analysis of miRNAs and lncRNAs.
  • Construction of a regulatory MLMI network using in silico prediction and experimental validation.
  • In vitro validation of the role of MEG3 in the MLMI network.

Main Results:

  • Identified 203 miRNAs and 1,090 lncRNAs, with 16 miRNAs and 3 lncRNAs significantly differentially expressed in HCC.
  • DE RNAs were enriched in 21 HCC-implicated pathways (e.g., p53, MAPK, NAFLD signaling).
  • Constructed the first comprehensive MLMI network for HCC, detailing interactions between 16 miRNAs, 3 lncRNAs, and 253 mRNAs.
  • Overexpression of MEG3 in vitro altered expression of targeted miRNAs and mRNAs, confirming its role.

Conclusions:

  • The constructed MLMI network provides a comprehensive view of synergistic modulation in hepatocarcinogenesis.
  • The identified ncRNA interactions offer novel molecular insights into HCC development.
  • This network-based approach presents a new avenue for understanding liver cancer mechanisms.

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