Bioinformatics analysis of gene expression alterations in microRNA‑122 knockout mice with hepatocellular carcinoma.

Abstract

Reduced microRNA (miR)-122 expression levels are frequently observed in hepatocellular carcinoma (HCC). The present study was conducted to investigate potential targets of miR-122 and determine the underlying regulatory mechanisms of miR-122 in HCC development. The public dataset GSE31731 was utilized, consisting of 8 miR-122 knockout (KO) mice (miR-122 KO) and 8 age-matched wild-type mice (WT group). Following data preprocessing, the differentially expressed genes (DEGs) were selected, followed by enrichment analysis. A protein-protein interaction (PPI) network was established, and a module network was further extracted. Combining the DEGs with microRNA targeting databases permitted the screening of the overlapping targets of miR-122. Furthermore, previously reported genes were screened out by literature mining. Transcription factors (TFs) of the targets were subsequently investigated. DEGs between miR-122 KO and WT groups were selected, including 713 upregulated and 395 downregulated genes. Of these, upregulated genes were enriched in cell cycle-associated processes [including nucleolar and spindle associated protein 1 (NUSAP1)], the cytokine-cytokine receptor interaction pathway [including C-X-C motif chemokine receptor 4 (CXCR4) and C-C motif chemokine receptor 2 (CCR2)], and the extracellular matrix-receptor interaction pathway [including integrin subunit alpha V (ITGAV)]. In addition, multiple overlapping targets were highlighted in the PPI network, including NUSAP1, CXCR4, CCR2 and ITGAV. Notably, CXCR4 and CCR2 were linked in module C, enriched in the cytokine-cytokine receptor interaction pathway. Furthermore, upregulated sex determining region Y-box 4 (SOX4) was identified as a TF. The results of the present study may provide a theoretical basis for further studies on the mechanisms of miR-122 in the development of HCC.