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
Agingauthors
Li Z,Lou Y,Tian G,Wu J,Lu A,Chen J,Xu B,Shi J,Yang Jdoi
10.18632/aging.102579subject
Has Abstractpub_date
2019-12-18 00:00:00pages
12375-12411issue
24issn
1945-4589pii
102579journal_volume
11pub_type
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