Dataset Information

Alterations in MicroRNA gene expression profile in liver transplant patients with hepatocellular carcinoma.

ABSTRACT:

Background

Hepatocellular carcinoma (HCC) can lead to liver failure which renders to liver transplant. miRNAs might be detected as biomarkers in subclinical stage of several hepatobiliary disorders like HCC. Therefore, in the present study, alterations in miRNAs as biomarkers were detected in LT patients with HCC.

Methods

Fourteen tissue samples composed of 5 rejected and 9 non-rejected ones were used for studying the miRNAs expression pattern using LNA-array probe assay and the result was evaluated by in house SYBR Green Real-time PCR protocols on 30 other tissue samples composed of 10 rejected and 20 non-rejected ones for the selected miRNAs. All samples were collected from liver transplanted patients with HCC.

Results

The study results revealed that in rejected patients compared to non-rejected ones, hsa-miR-3158-5p, -4449, -4511, and -4633-5p were up-regulated and hsa-miR-122-3p, -194-5p, 548as-3p, and -4284 were down-regulated. ROC curve analysis also confirmed that miR194-5p and -548as-3p in up-regulated and also, miR-3158-5p, -4449 in down-regulated microRNAs are significantly important molecules in rejection.

Conclusion

Finally, the tissue levels of specific miRNAs (especially hsa-miR-3158-5p, -4449, -194-5p and -548as-3p) significantly correlated with the development of HCC, which can be present as biomarkers after further completing studies.

SUBMITTER: Afshari A

PROVIDER: S-EPMC8199419 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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. 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.To 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.Eight 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.Our data indicates that the unique 7 miRNAs expression signature could be involved in the development HBV- related HCC.