Multi-omics Data Integration Reveals Novel Drug Targets in Hepatocellular Carcinoma

Overview

Journal BMC Genomics

Publisher Biomed Central

Specialty Genetics

Date 2021 Aug 5

PMID 34348664

Citations 6

Authors

Christos Dimitrakopoulos

Sravanth Kumar Hindupur

Marco Colombi

Dritan Liko

Charlotte K Y Ng

Salvatore Piscuoglio

Jonas Behr

Ariane L Moore

Jochen Singer

Hans-Joachim Ruscheweyh

Matthias S Matter

Dirk Mossmann

Luigi M Terracciano

Michael N Hall

Niko Beerenwinkel

Affiliations

Soon will be listed here.

Abstract

Background: Genetic aberrations in hepatocellular carcinoma (HCC) are well known, but the functional consequences of such aberrations remain poorly understood.

Results: Here, we explored the effect of defined genetic changes on the transcriptome, proteome and phosphoproteome in twelve tumors from an mTOR-driven hepatocellular carcinoma mouse model. Using Network-based Integration of multi-omiCS data (NetICS), we detected 74 'mediators' that relay via molecular interactions the effects of genetic and miRNA expression changes. The detected mediators account for the effects of oncogenic mTOR signaling on the transcriptome, proteome and phosphoproteome. We confirmed the dysregulation of the mediators YAP1, GRB2, SIRT1, HDAC4 and LIS1 in human HCC.

Conclusions: This study suggests that targeting pathways such as YAP1 or GRB2 signaling and pathways regulating global histone acetylation could be beneficial in treating HCC with hyperactive mTOR signaling.

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Arginine reprograms metabolism in liver cancer via RBM39.

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