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

First Author  Dimitrakopoulos C Year  2021
Journal  BMC Genomics Volume  22
Issue  1 Pages  592
PubMed ID  34348664 Mgi Jnum  J:310973
Mgi Id  MGI:6764765 Doi  10.1186/s12864-021-07876-9
Citation  Dimitrakopoulos C, et al. (2021) Multi-omics data integration reveals novel drug targets in hepatocellular carcinoma. BMC Genomics 22(1):592
abstractText  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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