Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Medical Biochemistry

Non-alcoholic fatty liver disease is a major chronic liver disease that can lead to liver cirrhosis, liver cancer, and ultimately death. Non-invasive biomarkers are urgently needed for patients with nonalcoholic steatohepatitis (NASH) to assist in diagnosis, monitoring disease progression and assessing treatment response. Aim of work: To assess (1) the correlation between circRNA-HIPK3 and miRNA-29a expression and its role as miRNA-29a sponge, (2) the correlation between circRNA-0046367 and each of miRNA-122 and miRNA-34a expression and its role as miRNA-122 and miRNA-34a sponge, and (3) the effect of miRNA-29a, miRNA-34a and miRNA-122 expression on wnt/Ý catenin pathway. Methods: The present study was conducted on 110 subjects of matched age and sex, subjects were classified into two groups: group (I): Fifty five healthy donors served as controls and group (II): Fifty five patients with fatty liver pattern in abdominal ultrasound. Lipid profile and liver functions were assessed. RT-PCR was done for assessed RNAs: circRNA-HIPK3, CircRNA-0046367, miRNA-29a, miRNA-122, miRNA-34a and Wnt mRNA gene expression. ELISA technique was performed for Ý-catenin protein levels.Results: Serum lipid abnormalities in the form of elevated total cholesterol, triglycerides and LDL-c levels, and reduced HDL-c levels were significantly detected in the patients group as opposed to controls (p <0.0001). Serum hepatic transaminases and total bilirubin were found to be significantly higher in the patients as compared to controls (p <0.0001 and 0.03 respectively). There was significant decrease in wnt1 gene expression (p <0.0001). Also there was significant increase in circRNA-HIPK3 expression concurrent with significant decrease in miRNA-29a expression (p <0.0001). There was significant decrease in circRNA-0046367 expression associated with significant increase in miRNA-34a expression (p <0.0001). There was significant decrease in miRNA-122 expression in patients group with p value <0.0001, and significant decrease in Ý-catenin protein level in patient group with p value 0.02. Conclusion: CircRNA-HIPK3 can be considered as miRNA-29a sponge while circRNA-0046367 can be considered as miRNA-34a sponge. Both miRNAs (29a and 34a) affect the wnt/Ý catenin pathway in NASH patients, and thus can be used as therapeutic targets for the disease

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