Research Article | Open Access | 10.31586/Biomedicine.0304.03

Expression Profiles Analysis Identification and Interaction of Key Genes and Micrornas in Hepatocellular Carcinoma

  • Jie Li1,2, Mi Li1, Zhiyuan Zhang1,* and Huan Zhao1,*
    Tianjin International Joint Academy of Biomedicine, Tianjin, China
    Wenshan Middle School, Yanshan Road, Changyi City, Shandong Province, China


Background: Hepatocellular carcinoma is one of the most common malignant tumors, with rapid development and high malignancy. MicroRNAs have been reported to play important roles in hepatocellular carcinoma progression. Aim: To identify the key genes and miRNAs in HCC, and to explore their potential molecular mechanisms. Methods: Gene expression profiles of GSE15471 (mRNA profile) and GSE57555 (miRNA profile) were downloaded from gene expression omnibus, which were analysed using R software and bioconductor packages. The gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichments of DEGs were performed using the DAVID database, and the protein–protein interaction networks of the DEGs were constructed from the STRING database. In addition, targets of differentially expressed miRNAs were predicted by the online resource miRDB. Result: In total, 191 differentially expressed genes were identified, including 142 upregulated and 49 downregulated genes. Functional analysis revealed that these DEGs were associates with wound healing, endodermal cell-cell adhesion, activation of MAPK activity and negative regulation of cell proliferation. In addition, we identified five DEMs, which were upregulated and downregulated. hsa-miR-122-5p may target the PDK4, and hsa-miR-21-5p probably targets SPOCK1 and PAIP2B. Conclusions: We applied integrated bioinformatics to identify key pathogenic genes involved in hepatocellular carcinoma and provide new clues for further studies of hepatocellular carcinoma.

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Feng Y, Zu LL, Zhang L. MicroRNA-26b inhibits the tumor growth of human liver cancer through the PI3K/Akt and NF-kappaB/MMP-9/VEGF pathways. Oncol Rep. 2018;39(5):2288-96.
Liu H, Cheng L, Cao D, Zhang H. Suppression of miR-21 Expression Inhibits Cell Proliferation and Migration of Liver Cancer Cells by Targeting Phosphatase and Tensin Homolog (PTEN). Med Sci Monit. 2018;24:3571-7.
Grainger S, Traver D, Willert K. Wnt Signaling in Hematological Malignancies. Prog Mol Biol Transl Sci. 2018;153:321-41.
Setshedi M, Andersson M, Kgatle MM, Roberts L. Molecular and cellular oncogenic mechanisms in hepatocellular carcinoma. S Afr Med J. 2018;108(8b):41-6.
Kroemer G, Pouyssegur J. Tumor cell metabolism: cancer's Achilles' heel. Cancer cell. 2008;13(6):472-82.
Lu X, Kang Y. Hypoxia and hypoxia-inducible factors: master regulators of metastasis. Clin Cancer Res. 2010;16(24):5928-35.
Guo JR, Shen HC, Liu Y, Xu F, Zhang YW, Shao Y, et al. Effect of Acute Normovolemic Hemodilution Combined with Controlled Low Central Venous Pressure on Blood Coagulation Function and Blood Loss in Patients Undergoing Resection of Liver Cancer Operation. Hepatogastroenterology. 2015;62(140):992-6.
Sang L, Wang XM, Xu DY, Zhao WJ. Bioinformatics analysis of aberrantly methylated-differentially expressed genes and pathways in hepatocellular carcinoma. World J Gastroenterol. 2018;24(24):2605-16.
He JH, Han ZP, Wu PZ, Zou MX, Wang L, Lv YB, et al. Gene-gene interaction network analysis of hepatocellular carcinoma using bioinformatic software. Oncol Lett. 2018;15(6):8371-7.
Dang S, Zhou J, Wang Z, Wang K, Dai S, He S. MiR-299-3p functions as a tumor suppressor via targeting Sirtuin 5 in hepatocellular carcinoma. Biomed Pharmacother. 2018;106:966-75.
Wakasugi H, Takahashi H, Niinuma T, Kitajima H, Oikawa R, Matsumoto N, et al. Dysregulation of miRNA in chronic hepatitis B is associated with hepatocellular carcinoma risk after nucleos(t)ide analogue treatment. Cancer Lett. 2018;434:91-100.
Li Z, Xue TQ, Yang C, Wang YL, Zhu XL, Ni CF. EGFL7 promotes hepatocellular carcinoma cell proliferation and inhibits cell apoptosis through increasing CKS2 expression by activating Wnt/beta-catenin signaling. J Cell Biochem. 2018;10.1002
Yan L, Xu F, Dai CL. Relationship between epithelial-to-mesenchymal transition and the inflammatory microenvironment of hepatocellular carcinoma. J Exp Clin Cancer Res. 2018;37(1):203.
Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001;22(2):153-83.
Li D, Ren W, Jiang Z, Zhu L. Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury. Mol Med Rep. 2018.
Si L, Xu L, Yin L, Qi Y, Han X, Xu Y, et al. Potent effects of dioscin against pancreatic cancer via miR-149-3P-mediated inhibition of the Akt1 signalling pathway. Br J Pharmacol. 2017;174(7):553-68.
Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science. 2001;294(5543):862-4.
Woolbright BL, Choudhary D, Mikhalyuk A, Trammel C, Shanmugam S, Abbott E, et al. The Role of Pyruvate Dehydrogenase Kinase-4 (PDK4) in Bladder Cancer and Chemoresistance. Mol Cancer Ther. 2018;17(9):2004-12.
Sun S, Liu J, Zhao M, Han Y, Chen P, Mo Q, et al. Loss of the novel mitochondrial protein FAM210B promotes metastasis via PDK4-dependent metabolic reprogramming. Cell Death Dis. 2017;8(6):e2870.
Choiniere J, Wu J, Wang L. Pyruvate Dehydrogenase Kinase 4 Deficiency Results in Expedited Cellular Proliferation through E2F1-Mediated Increase of Cyclins. Mol Pharmacol. 2017;91(3):189-96.
Han H, Li W, Shen H, Zhang J, Zhu Y, Li Y. microRNA-129-5p, a c-Myc negative target, affects hepatocellular carcinoma progression by blocking the Warburg effect. J Mol Cell Biol. 2016.
Yang J, Yang Q, Yu J, Li X, Yu S, Zhang X. SPOCK1 promotes the proliferation, migration and invasion of glioma cells through PI3K/AKT and Wnt/beta-catenin signaling pathways. Oncol Rep. 2016;35(6):3566-76.
Chen D, Zhou H, Liu G, Zhao Y, Cao G, Liu Q. SPOCK1 promotes the invasion and metastasis of gastric cancer through Slug-induced epithelial-mesenchymal transition. J Cell Mol Med. 2018;22(2):797-807.
Veenstra VL, Damhofer H, Waasdorp C, Steins A, Kocher HM, Medema JP, et al. Stromal SPOCK1 supports invasive pancreatic cancer growth. Mol Oncol. 2017;11(8):1050-64.
Kachaev ZM, Lebedeva LA, Kozlov EN, Toropygin IY, Schedl P, Shidlovskii YV. Paip2 is localized to active promoters and loaded onto nascent mRNA in Drosophila. Cell Cycle. 2018;17(14):1708-20.
Rosenfeld AB. Suppression of cellular transformation by poly (A) binding protein interacting protein 2 (Paip2). PLoS One. 2011;6(9):e25116.
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