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Discovering master regulators in hepatocellular carcinoma: one novel MR, SEC14L2 inhibits cancer cells

Zhihui Li1, Yi Lou1,2, Guoyan Tian1

  • 1Translational Medicine Center, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.

Aging
|December 19, 2019
PubMed

Insights

Researchers identified key master regulator (MR) genes in hepatocellular carcinoma (HCC) by analyzing 21 studies. A novel MR, SEC14L2, showed potential for targeted HCC therapy by suppressing tumor growth.

Area of Science:

  • Genomics
  • Cancer Biology
  • Bioinformatics

Background:

  • Master regulator (MR) gene identification aids in understanding disease-specific molecular programs.
  • A lack of consensus on commonly altered MRs in hepatocellular carcinoma (HCC) necessitates comprehensive analysis.

Purpose of the Study:

  • To identify commonly deregulated genes and master regulators (MRs) in hepatocellular carcinoma (HCC).
  • To assess the prognostic predictive capacity of identified HCC MRs and their regulons.
  • To uncover novel MRs for potential therapeutic interventions in HCC.

Main Methods:

  • Compiled and analyzed a compendium of 21 HCC datasets.
  • Employed reverse engineering of transcriptional networks to identify MRs.
  • Validated MRs using cross-validation in HCC datasets and patient-derived data.

Main Results:

  • Identified a comprehensive HCC signature of 483 commonly deregulated genes.
  • Confirmed prognostic predictive capabilities for most identified HCC MRs and their regulons.
  • Discovered a novel MR, SEC14L2, with anti-proliferative effects on HCC cells and tumor suppression in a mouse model.

Conclusions:

  • The study provides a comprehensive signature and identifies key MRs involved in HCC development and progression.
  • Network analyses revealed coordinated interactions among HCC MRs.
  • The novel MR SEC14L2 presents a potential therapeutic target for HCC interventions.
Keywords:
SEC14L2liver cancermaster regulatortranscriptional network

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