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.

SUBMITTER: He B 

PROVIDER: S-EPMC5436154 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature