Identification and functional analysis of key microRNAs in HBV-associated hepatocellular carcinoma

Abstract

Abstract: Objective: To investigate the hub microRNA of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and its effect on the proliferation and migration ability of HCC cells. Methods: ①The GEO2R tool was used to analyze the GSE69580 and GSE67882 datasets in the GEO database to screen for differentially expressed miRNAs (DEMs) between HBV-related HCC tissues and normal liver tissues. ②The miRTarBase database was used to predict the target genes of miRNAs and the DAVID database was used to target DEMs Gene annotation analysis of gene ontology (GO) and enrichment analysis of Kyoto Gene and Genome Encyclopedia (KEGG) pathway. ③Protein-protein interaction (PPI) network analysis was used to identify hub miRNAs of DEMs and the miRNACancerMAP database was used to analyze the signal pathways that miRNAs might be involved in. ④Kaplan-Meier Plotter database was used to analyze the relationship between hub miRNAs and HCC clinical prognosis. ⑤MTT method and scratch experiments were used to verify the effect of DEMs on the proliferation and migration of HCC cells. Results: A total of 12 up-regulated DEMs and one down-regulated DEM were identified by bioinformatics analysis, and GO and KEGG functional enrichment analysis indicated that miR-93 and miR-125b were involved in tumor-associated signaling pathways such as MAPK, PI3K-AKT, and P53. Kaplan-Meier plotter survival analysis revealed that miR-93 expression level was negatively correlated with the prognosis of patients with HBV-related HCC (P=0.036), while miR-125b expression level was positively correlated with the prognosis of patients with HBV-related HCC (P=0.032). In HBsAg-positive hepatocellular carcinoma cell line MHCC-97H, overexpression of miR-93 or inhibition of miR-125b increased the proliferation and migration capacity of MHCC-97H cells (P<0.05), while overexpression of miR-125b or inhibition of miR-93 decreased the proliferation and migration capacity of MHCC-97H cells (P<0.05). Conclusion: miR-93 and miR-125b are the hub miRNAs for HBV-associated HCC, and up-regulation of miR-125b or down-regulation of miR-93 inhibited the proliferation and migration capacity of the hepatocellular carcinoma cell line MHCC-97H.

Key words: Hepatocellular carcinoma, MicroRNA, Proliferation, Prognosis

Pei Zhiyan, Wang Jianli, Zhang Lingyi. Identification and functional analysis of key microRNAs in HBV-associated hepatocellular carcinoma[J]. Electronic Journal of Liver Tumor, 2020, 7(4): 29-37.

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