Dataset Information

Discovering master regulators in hepatocellular carcinoma: one novel MR, SEC14L2 inhibits cancer cells.

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.

SUBMITTER: Li Z

PROVIDER: S-EPMC6949064 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Discovering master regulators in hepatocellular carcinoma: one novel MR, SEC14L2 inhibits cancer cells.

Li Zhihui Z Lou Yi Y Tian Guoyan G Wu Jianyue J Lu Anqian A Chen Jin J Xu Beibei B Shi Junping J Yang Jin J

Aging 20191218 24

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 develo ...[more]

PMID: 31851620

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Project description:Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and rapidly lethal tumors. However, limited advances have been made to prolong the survival and to reduce the mortality over the last decades. Therefore, identifying the master regulators underlying ATC progression is desperately needed. In our present study, three datasets including GSE33630, GSE29265, and GSE65144 were retrieved from Gene Expression Omnibus with a total of 32 ATC samples and 78 normal thyroid tissues. A total of 1804 consistently changed differentially expressed genes (DEGs) were identified from three datasets. KEGG pathways enrichment suggested that upregulated DEGs were mainly enriched in ECM-receptor interaction, cell cycle, PI3K-Akt signaling pathway, focal adhesion, and p53 signaling pathway. Furthermore, key gene modules in PPI network were identified by Cytoscape plugin MCODE and they were mainly associated with DNA replication, cell cycle process, collagen fibril organization, and regulation of leukocyte migration. Additionally, TOP2A, CDK1, CCNB1, VEGFA, BIRC5, MAPK1, CCNA2, MAD2L1, CDC20, and BUB1 were identified as hub genes of the PPI network. Interestingly, module analysis showed that 8 out of 10 hub genes participated in Module 1 network and more than 70% genes of Module 2 consisted of collagen family members. Notably, transcription factors (TFs) regulatory network analysis indicated that E2F7, FOXM1, and NFYB were master regulators of Module 1, while CREB3L1 was the master regulator of Module 2. Experimental validation showed that CREB3L1, E2F7, and FOXM1 were significantly upregulated in ATC tissue and cell line when compared with normal thyroid group. In conclusion, the TFs regulatory network provided a more detail molecular mechanism underlying ATC occurrence and progression. TFs including E2F7, FOXM1, CREB3L1, and NFYB were likely to be master regulators of ATC progression, suggesting their potential role as molecular therapeutic targets in ATC treatment.

Dataset Information

Discovering master regulators in hepatocellular carcinoma: one novel MR, SEC14L2 inhibits cancer cells.

Publications

Discovering master regulators in hepatocellular carcinoma: one novel MR, SEC14L2 inhibits cancer cells.

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