Multi-omics data integration reveals novel drug targets in hepatocellular carcinoma.
HCC
NetICS
Omics
mTOR signaling
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
04 Aug 2021
04 Aug 2021
Historique:
received:
11
03
2021
accepted:
06
07
2021
entrez:
5
8
2021
pubmed:
6
8
2021
medline:
7
8
2021
Statut:
epublish
Résumé
Genetic aberrations in hepatocellular carcinoma (HCC) are well known, but the functional consequences of such aberrations remain poorly understood. 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. 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.
Sections du résumé
BACKGROUND
BACKGROUND
Genetic aberrations in hepatocellular carcinoma (HCC) are well known, but the functional consequences of such aberrations remain poorly understood.
RESULTS
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
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.
Identifiants
pubmed: 34348664
doi: 10.1186/s12864-021-07876-9
pii: 10.1186/s12864-021-07876-9
pmc: PMC8340535
doi:
Substances chimiques
MicroRNAs
0
Pharmaceutical Preparations
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
592Subventions
Organisme : ERC Synergy Grant
ID : 609883
Organisme : SystemsX.ch RTD Grant
ID : 2013/150
Organisme : EC Horizon 2020 project SOUND
ID : 633974
Informations de copyright
© 2021. The Author(s).
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