Circular SERPINA3 and its target microRNA-944 as potential biomarkers in hepatitis C virus-induced hepatocellular carcinoma in Egyptian population

Nora M Aborehab; Mohamed A Kandeil; Dina Sabry; Radwa Rabie; Ibrahim T Ibrahim

doi:10.1016/j.ncrna.2023.05.005

Circular SERPINA3 and its target microRNA-944 as potential biomarkers in hepatitis C virus-induced hepatocellular carcinoma in Egyptian population

Noncoding RNA Res. 2023 May 23;8(3):401-412. doi: 10.1016/j.ncrna.2023.05.005. eCollection 2023 Sep.

Authors

Nora M Aborehab¹, Mohamed A Kandeil², Dina Sabry^{3

4}, Radwa Rabie¹, Ibrahim T Ibrahim⁵

Affiliations

¹ Department of Biochemistry, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, 12451, Egypt.
² Department of Biochemistry, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, 62521, Egypt.
³ Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Badr University in Cairo, Cairo, 11829, Egypt.
⁴ Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, 11562, Egypt.
⁵ Department of Biochemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62521, Egypt.

Abstract

Background: The most prevalent cancer in Egypt is hepatocellular carcinoma (HCC) mainly due to the infection with the hepatitis C virus. So it is critical to find sensitive biomarkers for early diagnosis of HCC and avoid post-operation tumor recurrence. Therefore, this research was designed to demonstrate the circSERPINA3 role in the regulation of microRNA-944 gene expression in HCV-related HCC cases and compare these results with circSERPINA3 and microRNA-944 gene expression levels in HCV-infected patients.

Methodology: Study participants were divided into three groups: healthy controls, HCV- infected, and HCV-induced HCC patients. The gene expression levels of circSERPINA3 and microRNA-944 were evaluated using Real-Time qPCR. Then the immunoblotting procedure was applied to measure the serum levels of MDM2 and E-cadherin besides, the serum concentration levels of glypican-3 and alpha-fetoprotein were measured by sandwich ELISA.

Results: The gene expression level of circSERPINA3 was significantly upregulated in both HCV-infected and HCC patients causing suppression of the antitumor effect of miR-944 and showing a lower 1-year survival rate than the participants who had low circSERPINA3 gene expression levels. Subsequently, the miR-944 downstream protein, MDM2 was remarkably upregulated, exaggerating the metastasis and oxidative stress in HCC cases. Additionally, the results confirmed the downregulation of microRNA-944 improved the progression of viral hepatitis C cases to hepatocarcinogenesis through the significantly increased serum level of the metastatic marker, E-cadherin. Although alpha-fetoprotein is a common diagnostic marker used in the diagnosis of HCC, our results showed that glypican-3 had greater sensitivity and specificity and positively correlated to the IGF-1 signaling pathway of HCC cases. Moreover, the gene expression levels of circSERPINA3 and E-cadherin in both the HCV and HCV-induced HCC were significantly positively correlated.

Conclusion: circSERPINA3 and miR-944 were sensitive molecular markers for early diagnosis of HCC and could be prospective treatment targets for HCV-infected patients to avoid tumor recurrence in HCC cases.

Keywords: CircSERPINA3; Glypican-3; Hepatitis C; Metastasis; miR-944.