The Emerging Role of Circular RNA Homeodomain Interacting Protein Kinase 3 and Circular RNA 0046367 through Wnt/Beta-Catenin Pathway on the Pathogenesis of Nonalcoholic Steatohepatitis in Egyptian Patients

Abstract

Background: Non-alcoholic fatty liver disease is a major problem worldwide that needs non-invasive biomarkers for early diagnosis and treatment response assessment. We aimed to assess the correlation between circRNA-HIPK3 and miRNA-29a expression and its role as miRNA-29a sponge, as well as the correlation between circRNA-0046367 and miRNA-34a expression and its role as miRNA-34a sponge and their effect on regulation of the Wnt/β catenin pathway, which may provide a new target for treatment of non-alcoholic steatohepatitis.

Methods: the research was performed on 110 participants: group (I): fifty-five healthy donors served as controls and group (II): fifty-five patients with fatty liver pattern on abdominal ultrasound. Lipid profile and liver functions were assessed. RT-PCR was performed to assess the RNAs: circRNA-HIPK3, circRNA-0046367, miRNA-29a, miRNA-34a and Wnt mRNA gene expression. ELISA was performed to determine β-catenin protein levels.

Results: miRNA-34a and circRNA-HIPK3 expression were significantly greater, while miRNA-29a and circRNA-0046367 expression were significantly less, in patients than in controls. Wnt/β-catenin regulated by miRNA-29a and miRNA-34a showed a significant decrease that leads to its abnormal effect on lipid metabolism.

Conclusions: our results imply that miRNA-29a can be investigated as a target for circRNA-HIPK3, while miRNA-34a can be investigated as a target for circRNA-0046367, and that circRNA-HIPK3 and circRNA-0046367 may have emerging roles that can affect the pathogenesis of nonalcoholic steatohepatitis through the Wnt/β-catenin pathway and thus be used as therapeutic targets for the disease.

Keywords: Circrna-HIPK3; Wnt/β-catenin NASH; circRNA-0046367; miRNA-29a; miRNA-34a.

Fig. 1

A : β-Catenin concentrations in patients and controls. B: RQ of targeted circular RNAs and Wnt1 expression in patients and controls. C: RQ of targeted miRNA expression in patients and controls.

Fig. 2

Variable were correlated using Spearman’s correlation coefficient. A: miRNA-29a and circRNA-HIPK3 expression were negatively correlated (r = 0.94, p < 0.0001). B: miRNA-34a and circRNA-0046367 expression were negatively correlated (r = 0.76, p < 0.0001). C: miRNA-29a and Wnt1 expression were positively correlated (r = 0.88, p < 0.0001). D: miRNA-34a and Wnt1 expression were negatively correlated (r = 0.71, p < 0.0001).