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

Abstract:

:Identification of master regulator (MR) genes offers a relatively rapid and efficient way to characterize disease-specific molecular programs. Since strong consensus regarding commonly altered MRs in hepatocellular carcinoma (HCC) is lacking, we generated a compendium of HCC datasets from 21 studies and identified a comprehensive signature consisting of 483 genes commonly deregulated in HCC. We then used reverse engineering of transcriptional networks to identify the MRs that underpin the development and progression of HCC. After cross-validation in different HCC datasets, systematic assessment using patient-derived data confirmed prognostic predictive capacities for most HCC MRs and their corresponding regulons. Our HCC signature covered well-established liver cancer hallmarks, and network analyses revealed coordinated interaction between several MRs. One novel MR, SEC14L2, exerted an anti-proliferative effect in HCC cells and strongly suppressed tumor growth in a mouse model. This study advances our knowledge of transcriptional MRs potentially involved in HCC development and progression that may be targeted by specific interventions.

journal_name

Aging (Albany NY)

journal_title

Aging

authors

Li Z,Lou Y,Tian G,Wu J,Lu A,Chen J,Xu B,Shi J,Yang J

doi

10.18632/aging.102579

subject

Has Abstract

pub_date

2019-12-18 00:00:00

pages

12375-12411

issue

24

issn

1945-4589

pii

102579

journal_volume

11

pub_type

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