Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recurrence of hepatocellular carcinoma (HCC) even after curative resection causes dismal outcomes of patients. Here, to delineate the driver events of genomic and transcription alteration during HCC recurrence, we performed RNA-Seq profiling of the paired primary and recurrent tumors from two patients with intrahepatic HCC. By comparing the mutational and transcriptomic profiles, we identified somatic mutations acquired by HCC recurrence including novel mutants of GOLGB1 (E2721V) and SF3B3 (H804Y). By performing experimental evaluation using siRNA-mediated knockdown and overexpression constructs, we demonstrated that the mutants of GOLGB1 and SF3B3 can promote cell proliferation, colony formation, migration, and invasion of liver cancer cells. Transcriptome analysis also revealed that the recurrent HCCs reprogram their transcriptomes to acquire aggressive phenotypes. Network analysis revealed CXCL8 (IL-8) and SOX4 as common downstream targets of the mutants. In conclusion, we suggest that the mutations of GOLGB1 and SF3B3 are potential key drivers for the acquisition of an aggressive phenotype in recurrent HCC.
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PMID:Mutations acquired by hepatocellular carcinoma recurrence give rise to an aggressive phenotype. 2803 42

Long noncoding RNA OIP5-AS1 has been observed to be increased in several cancers, however, its role and biological mechanism was poorly understood in HCC. Currently, we found OIP5-AS1 expression was upregulated in HCC cells compared with normal human liver cells. Knockdown of OIP5-AS1 suppressed HCC cell proliferation, induced cells cycle arrest and cells apoptosis. In addition, HCC cell migration and invasion capacity in vitro were also inhibited by OIP5-AS1 inhibition. Bioinformatics analysis revealed OIP5-AS1 could interact with miR-363-3p, thereby repressing HCC development. We also observed miR-363-3p was significantly decreased in HCC cells and overexpression of miR-363-3p repressed HCC progression. The correlation between OIP5-AS1 and miR-363-3p was confirmed by performing RIP assay and RNA pull-down assay. Subsequently, SOX4 was predicted as a target of miR-363-3p and miR-363-3p modulated SOX4 levels negatively in vitro. Apart from these, in vivo experiments established that OIP5-AS1 can suppress HCC development through regulating miR-363-3p and SOX4. Collectively, these demonstrated that OIP5-AS1 was involved in HCC progression via targeting miR-363-3p and SOX4. OIP5-AS1 can act as a novel candidate for HCC diagnosis, prognosis, and therapy.
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PMID:LncRNA OIP5-AS1 interacts with miR-363-3p to contribute to hepatocellular carcinoma progression through up-regulation of SOX4. 3204 27

BACKGROUND Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world. Bioinformatics studies have been widely used for screening genes involved in the initiation and progression of HCC. MATERIAL AND METHODS We obtained liver cancer microarray raw data from the GEO database (GSE54238). Next, weighted gene co-expression network analysis (WGCNA) was used to assess the critical modules. Then, we assessed the gene significance by calculating survival, expression level, and receiver operating characteristic (ROC) in the TCGA database. We also validated the expression of selected genes in the Oncomine database and calculated the relationship between 4 hub genes and immune infiltration. Finally, GSEA enrichment analysis was used to explore the potential mechanism. RESULTS We identified the red and blue modules as the critical modules, and found 176 candidate genes by assessing gene significance. GO and KEEG results suggested that the candidate genes are involved in the cell cycle. Four hub genes - SOX4, STK39, TARBP1, and TDRKH - were eventually screened after validating their expression and power in diagnosing HCC in the TCGA database. Immune infiltration analysis and GSEA enrichment analysis showed that these 4 hub genes were correlated with the immune cell populations infiltration and that multiple mechanisms were involved, such as angiogenesis and epithelial-mesenchymal transition. CONCLUSIONS Our findings revealed that these 4 genes can be regarded as potential prognosticators and therapeutic targets for HCC.
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PMID:Identification of Hub Genes in Hepatocellular Carcinoma Related to Progression and Prognosis by Weighted Gene Co-Expression Network Analysis. 3220 Mar 87

The present study investigated whether microRNA (miR)-132-3p targeted transcription factor SOX-4 (Sox4) for the inhibition of proliferation, migration, invasion and promotion of apoptosis in liver cancer (LC) cells. The expression of miR132-3p and Sox4 mRNA was evaluated by quantitative PCR and protein expression was determined by western blot analysis. Cell proliferation, apoptosis, migration, and invasion were assessed at different time points by the MTT assay, flow cytometry analysis, wound healing assay and Transwell migration assay, respectively. Bioinformatics prediction and luciferase assays were performed to validate and confirm Sox4as a potential target of miR-132p. There was a reduced expression of miR-132-3p in HepG2 and Huh7 cell lines compared with HccLM3 cells. Overexpression of miR-132-3p resulted in significant inhibition of proliferation and induction of apoptosis in LC cells. Moreover, migration and invasion of HepG2 cells were suppressed by over expressing miR-132-3p. However, downregulation of miR-132-3p in Hep-G2 cells promoted cell growth, invasion and migration and inhibited apoptosis. Bioinformatics analysis predicted Sox4 as a potential target of miR-132-3p, which was further confirmed by the luciferase reporter assay. In addition, an inverse association was observed between miR-132-3p and Sox4 expression. miR-132-3p may regulate the proliferation, apoptosis, migration and invasion of HepG2 cells by targeting Sox4.
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PMID:MicroRNA-132-3p regulates cell proliferation, apoptosis, migration and invasion of liver cancer by targeting Sox4. 3225 13