RNA sequencing analysis reveals the competing endogenous RNAs interplay in resected hepatocellular carcinoma patients who received interferon-alpha therapy

Abstract

Abstract Background Interferon-alpha (IFN-α) is a general therapeutic regimen to be utilized in hepatocellular carcinoma (HCC). However, regulatory mechanisms of IFN-α on competing endogenous RNAs (ceRNAs) level in anti-HCC relapse are rarely understood. Methods HCC patients with and without IFN-α treatment were calculated to analyze the expression profile of mRNA, long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA) by RNA sequence, and significant differential expression (DE) of these types of RNAs were selected for further analysis. A ceRNA regulatory network was constructed to explore the potential mechanisms of IFN-α intervention on anti-HCC relapse. Finally, the potential prognostic associated genes among these DE RNAs were identified. Results Totally, 556 mRNAs, 120 circRNAs, 87 lncRNAs, and 96 miRNAs were differentially expressed in patients who received IFN-α treatment. A ceRNA regulatory network including a circRNA-miRNA-mRNA network which composed of 4 up- and 10 down-regulated circRNAs, 8 up- and 5 down-regulated miRNAs, 28 up- and 9 down-regulated mRNAs, and a lncRNA-miRNA-mRNA network which composed of 10 up- and 3 down-regulated lncRNAs, 11 up- and 5 down-regulated miRNAs, 28 up- and 10 down-regulated mRNAs was constructed. Gene enrichment and pathway analysis revealed that the ceRNA network was associated with immune-related pathway and corresponding molecular function in patients who accepted IFN-α treatment. Next, we identified 3 most relevant to IFN-α treatment to HCC among these DE RNAs, namely FAM20A, IGFBP4 and MARCH3, as the prognostic associated genes for HCC. Furthermore, MARCH3 expression correlated with infiltrating levels of tumor infiltrating immune cells (TICCs) in HCC. MARCH3 expression also showed strong correlations with the gene markers of diverse immune cells in HCC. Conclusion Our data discovered a novel ceRNA network in HCC patients receiving IFN-α therapy, which might lay the foundation for better understand the regulatory mechanism of IFN-α treatment.