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Multi-omics data integration reveals novel drug targets in hepatocellular carcinoma

by Mossmann, Dirk , Hindupur, Sravanth Kumar , Ng, Charlotte K. Y. , Hall, Michael N. , Behr, Jonas , Beerenwinkel, Niko , Dimitrakopoulos, Christos , Matter, Matthias S. , Colombi, Marco , Ruscheweyh, Hans-Joachim , Terracciano, Luigi M. , Piscuoglio, Salvatore , Singer, Jochen , Liko, Dritan , Moore, Ariane L.

in Acetylation / Animal Genetics and Genomics / Biomedical and Life Sciences / Cancer / Cell cycle / Cell growth / Cellular signal transduction / Data integration / Drug targeting / Drug therapy / Electronic data processing / Gene expression / Genetic aspects / Genomics / Grb2 protein / HCC / Hepatocellular carcinoma / Hepatoma / Histones / Human and rodent genomics / Integration / Kinases / Life Sciences / Liver cancer / Methods / Microarrays / Microbial Genetics and Genomics / MicroRNAs / miRNA / Molecular interactions / mTOR signaling / Mutation / NetICS / Omics / Oncology, Experimental / Phosphatase / Phosphorylation / Plant Genetics and Genomics / Proteins / Proteomes / Proteomics / Research Article / Signal transduction / Signaling / SIRT1 protein / Therapeutic targets / TOR protein / Transcription factors / Transcriptomes / Tumorigenesis / Tumors / Yes-associated protein

2021

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Multi-omics data integration reveals novel drug targets in hepatocellular carcinoma

2021

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2021

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Journal Article

Multi-omics data integration reveals novel drug targets in hepatocellular carcinoma

Mossmann, Dirk,

Hindupur, Sravanth Kumar,

Ng, Charlotte K. Y.,

Hall, Michael N.,

Behr, Jonas,

Beerenwinkel, Niko,

Dimitrakopoulos, Christos,

Matter, Matthias S.,

Colombi, Marco,

Ruscheweyh, Hans-Joachim,

Terracciano, Luigi M.,

Piscuoglio, Salvatore,

Singer, Jochen,

Liko, Dritan,

Moore, Ariane L.

2021

Overview

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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Publisher

BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC

Subject

Acetylation

/ Animal Genetics and Genomics

/ Biomedical and Life Sciences

/ Cancer

/ Cell cycle

/ Cell growth

/ Cellular signal transduction