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      Identification of key genes and related pathways in hepatocarcinoma using bioinformatics analysis

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          Abstract

          Highlights:The present study described the differently expressed genes between normal tissues and hepatocellular carcinoma tissues from the level of gene transcription. The possible signaling pathways involved in the development of hepatocellular carcinoma and related molecules involved were analyzed.

          Editor’s Summary:Bioinformatics analysis is an important tool for the analysis of tumor gene expression changes in the level of signaling pathways, which help provide direction for laboratory and clinical research.

          Objective: Various treatments have greatly reduced the mortality of hepatocellular carcinoma (HCC). However, few therapies could be performed in advanced HCC. Therefore, understanding the characteristics of HCC at the level of the whole transcriptome can help prevent the progression of HCC. Methods: The aim of this study was to identify differently expressed genes and potent pathways between normal liver and HCC tissues. The gene expression profiles of GSE104627 were downloaded from Gene Expression Omnibus database. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed and protein-protein interaction network of the differentially expressed genes were constructed by Cytoscape software. Results: In total, 880 differently expressed genes were identified between normal and tumor tissues, including 554 up-regulated genes and 326 down-regulated genes. Gene Ontology analysis results showed that the up-regulated genes were significantly enriched in establishment of RNA localization, nucleic acid transport, RNA transport, RNA localization and nucleobase, nucleoside, nucleotide and nucleic acid transport. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed the up-regulated genes were enriched in axon guidance, dorso-ventral axis formation and pathways in cancer. The top 10 hub genes were identified from the protein - protein interaction network, and sub-networks revealed these genes were involved in significant pathways, including G protein-coupled receptors signaling pathway, signaling pathway via MAPK and extracellular matrix organization. Conclusion: The present study described the differently expressed genes between normal tissues and HCC tissues from the level of gene transcription. The possible signaling pathways involved in the development of HCC and related molecules involved were analyzed. However, further laboratory and clinical validation is still needed.

          Most cited references16

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          Hepatocellular carcinoma in Asia: Prevention strategy and planning.

          To review all of epidemiological and etiological aspects of hepatocellular carcinoma (HCC) and examined the prevention of this disease in Asia.
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            Critical role of RanBP2-mediated SUMOylation of Small Heterodimer Partner in maintaining bile acid homeostasis

            Bile acids (BAs) are recently recognized signalling molecules that profoundly affect metabolism. Because of detergent-like toxicity, BA levels must be tightly regulated. An orphan nuclear receptor, Small Heterodimer Partner (SHP), plays a key role in this regulation, but how SHP senses the BA signal for feedback transcriptional responses is not clearly understood. We show an unexpected function of a nucleoporin, RanBP2, in maintaining BA homoeostasis through SUMOylation of SHP. Upon BA signalling, RanBP2 co-localizes with SHP at the nuclear envelope region and mediates SUMO2 modification at K68, which facilitates nuclear transport of SHP and its interaction with repressive histone modifiers to inhibit BA synthetic genes. Mice expressing a SUMO-defective K68R SHP mutant have increased liver BA levels, and upon BA- or drug-induced biliary insults, these mice exhibit exacerbated cholestatic pathologies. These results demonstrate a function of RanBP2-mediated SUMOylation of SHP in maintaining BA homoeostasis and protecting from the BA hepatotoxicity.
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              Pigment epithelium-derived factor promotes tumor metastasis through an interaction with laminin receptor in hepatocellular carcinomas

              Pigment epithelium-derived factor (PEDF) has complex functions in tumor metastasis, but little is known about the roles of PEDF and its receptors in hepatocellular carcinoma (HCC). Here we found that high expression of PEDF is associated with shorter overall survival in HCC patients. Forced expression of PEDF enhanced HCC cell aggressive behavior in vitro and in vivo, whereas silencing PEDF expression reduced migration and invasion. Furthermore, PEDF expression led to changes in cell morphology and the expression of epithelial–mesenchymal transition (EMT)-related markers via ERK1/2 signaling pathway, including the upregulation of N-cadherin and slug, and the downregulation of E-cadherin in HCC cells. Our results further showed that PEDF could interact with laminin receptor (LR) and LR knockdown attenuated PEDF-induced migration, invasion and the change of EMT-related markers. More importantly, in clinical HCC specimens, we found that PEDF expression was correlated with subcellular localization of LR, and that high expression of PEDF and positive expression of LR predicted a poor prognosis. In conclusion, our results demonstrate a novel functional role of PEDF/LR axis in driving metastasis through ERK1/2-mediated EMT in HCC and provided a promising prognostic marker in HCC.
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                Author and article information

                Contributors
                Journal
                TMR Editorial Board
                Traditional Medicine Research (Cancer)
                TMR Editorial Board (Jintang road, 99, Hedong district Tianjin,China, 300170 )
                2538-015X
                10 June 2018
                10 June 2018
                : 1
                : 2
                : 51-57
                Affiliations
                [1-2538-015X-1-2-51] 1Surgery Department of Tianjin Medical University General Hospital, Tianjin, China.
                [2-2538-015X-1-2-51] 2 Department of Pharmacology, Basic Medical College, Tianjin Medical University, Tianjin, China.
                Author notes
                *Correspondence to: Dan Chen, Department of Pharmacology, Basic Medical College, Tianjin Medical University, Tianjin, 300070, China. E-mail: ilvcd@ 123456163.com.

                Submitted: 20 April 2018, Accepted: 05 May 2018, Online: 10 May 2018.

                Abbreviations: HCC, Hepatocellular carcinoma; GO, Gene Ontology; DEGs, Differentially expressed genes; GEO, Gene Expression Omnibus; KEGG, Kyoto Encyclopedia of Genes and Genomes pathway; STRING, Search Tool for the Retrieval of Interacting Genes; PPI, Protein-protein interaction.

                Competing interests: Authors declare that they have no competing interests.

                Copyright: ©2018 TMR Publishing Group Limited. This is an open access article distributed under the terms of the Creative Commons Attribution Non Commercial License.

                Executive Editor: Yu-Chan Cao.

                Article
                2538-015X-1-2-51
                10.12032/TMRC201800029
                486391e9-452f-4814-9ec4-f4c246ec48cf

                This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 5 May 2018
                Categories
                Orginal Article

                Medicine,Pharmacology & Pharmaceutical medicine,Health & Social care,Complementary & Alternative medicine
                Hepatocarcinoma,Bioinformatics analysis,Differently expressed genes

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