Abstract
BackgroundMicroRNAs (miRNAs) exhibit essential regulatory functions related to cell growth, apoptosis, development and differentiation. Dysregulated expression of miRNAs is associated with a wide variety of human diseases. As such miRNA signatures are valuable as biomarkers for disease and for making treatment decisions. Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Here we screened for miRNAs in chronic HBV associated HCC.MethodsTo determine the miRNAs in HCC occurrence associated with HBV infection, we analyzed global miRNA expression profiles in 12 pairs of HCC and adjacent matched non-HCC tissues from HBV-positive and HBV-negative patients using microarray analyses. The microarray result was validated by real-time PCR in 32 HBV-positive and 24 HBV-negative patient HCC samples. The potential candidate target genes of the miRNAs were predicted by miRWalk software. Genes simultaneously predicted as targets by two or more miRNAs were subjected to GO and KEGG pathway analysis. The miRNA regulatory network analysis was performed using the Ingenuity Pathway Analysis (IPA) software.ResultsEight miRNAs (miR-223, miR-98, miR-15b, miR-199a-5p, miR-19b, miR-22, miR-451, and miR-101) were involved in HBV-unrelated HCC, 5 miRNAs (miR-98, miR-375, miR-335, miR-199a-5p, and miR-22) were involved in HBV infection, and 7 miRNAs (miR-150, miR-342-3p, miR-663, miR-20b, miR-92a-3p, miR-376c-3p and miR-92b) were specifically altered in HBV-related HCC. Gene Ontology and KEGG analyses predict that these HBV-related HCC miRNAs are involved in the regulation of: transcription, RNA polymerase II promoter, phosphorylation of proteins through MAPK signaling pathway, focal adhesion, and actin cytoskeleton. IPA analysis also suggest that these miRNAs act on AGO2, TP53, CCND1, and 11 other genes that significantly influence HCC occurrence and HBV infection.ConclusionOur data indicates that the unique 7 miRNAs expression signature could be involved in the development HBV- related HCC.
Highlights
MicroRNAs exhibit essential regulatory functions related to cell growth, apoptosis, development and differentiation
By miRNA expression profile, we found that miR-150, miR-342-3p, miR-663, miR-20b, miR-92a3p, miR-376c-3p, and miR-92b are altered in Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC)
Using ANOVA to screen the differential expression of miRNAs at P-value ≤ 0.01, fold change ≥ 2 or ≤ 0.5, 225 miRNAs were detected (Additional file 1: Figure S1). This finding suggests that HBV infection may affect the expression of miRNAs in liver cells, and the changes in miRNA expression may result in specific inflammation and tumorigenesis
Summary
MicroRNAs (miRNAs) exhibit essential regulatory functions related to cell growth, apoptosis, development and differentiation. Dysregulated expression of miRNAs is associated with a wide variety of human diseases. Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). MicroRNAs (miRNA) constitute a recently discovered class of non-coding RNAs and are known to function in the regulation of gene expression [7, 8]. These molecules regulate the expression of as much as 30% of all. Wang et al BMC Cancer (2017) 17:805 mammalian protein-encoding genes In addition to their important roles in healthy individuals, many studies have revealed that various miRNAs are involved in human carcinogenesis and other diseases. There is a paucity of information on miRNAs engaged in HBV-related HCC and the regulatory mechanisms of these miRNAs remain largely unknown
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