Identification of miRNAs, mRNAs, lncRNAs, and circRNAs associated with hepatocellular carcinoma recurrence after interferon treatment

Abstract

To study the molecular mechanism of interferon-alpha (IFN-α) in the treatment of hepatocellular carcinoma (HCC) and the molecular markers that can predict the therapeutic effect, differentially expressed (DE)-miRNAs, -mRNAs, -lncRNAs, and -circRNAs were screened between 12 samples collected from 4 patients who had not received treatment (control), 4 patients who had received recombinant human interferon a-2b treatment (case1), and 4 patients who had relapsed after receiving recombinant human interferon a-2b treatment (case2). Enrichment analyses were performed to determine the principal functions of the DE-RNAs. We also constructed protein-protein interactions (PPI) and competing endogenous RNA (ceRNA) networks. In addition, a series-cluster analysis was performed to analyze changes in gene expression across different groups of HCC. Furthermore, the expression of the genes were verified in the Cancer Genome Atlas (TCGA) database. A total of 36 union DE-miRNAs, 175 union DE-mRNAs, 65 union DE-lncRNAs, and 52 union DE-circRNAs were obtained between the control vs case1, and case2 vs case1 groups. DE-mRNAs were mainly involved in the mitochondrial inner membrane. DE-circRNAs were mainly enriched in the Golgi apparatus. ceRNA network contained 68 DE-mRNAs, 26 DE-miRNAs, 45 DE-lncRNAs, and 23 DE-circRNAs. A total of 24 DE-miRNAs, 175 DE-mRNAs, 65 DE-lncRNAs, and 52 DE-circRNAs were classified into eight profiles, respectively. A total of 26 genes showed a significant correlation with prognosis of HCC (p < 0.05). Some genes may be used to predict the efficacy of IFN-α in the treatment of HCC. The results may lay a foundation for investigating the different sensitivities of IFN-α in the treatment of HCC.

Keywords: competing endogenous RNA; differentially expressed genes; hepatocellular carcinoma; protein to protein interaction network; series-cluster analysis.