FOXA2 DNA Binding Domain Mutation and MiRNA-124 Differential Expression in Relation to Sexual Dimorphism of Hepatocellular Carcinoma in Egyptian Patients.

Hepatocellular carcinoma (HCC) is sexually dimorphic in mammals. Forkhead box A2 (FOXA2) binding sites’ mutations exhibited impairment in binding between FOXA2, hormonal receptors and their target genes. Recent studies of microRNA (miRNA) expression have demonstrated miRNA-124 dysregulation in hepatocellular carcinoma (HCC). Molecular mechanism underlying sexual dimorphism remains unclear. Here, we investigated FOXA2 DNA binding domain (DBD) polymorphism and the status of miRNA-124 expression in Egyptian patients. Patients/Methods: 78 patients were classified into three groups equally matched in sex; HCC, cirrhotic and control subjects. Direct Sequencing of FOXA2 DBD was conducted, followed by mutation frequency calculations. Quantitative Real-time PCR method was used to assess the expression levels of miR-124. Results: Two detected significant single nucleotide polymorphisms (SNPs), (c.3699G>T) and (c.3708G>T) were identified in FOXA2 DBD of 14% and 7%, respectively in both HCC and cirrhotic cases. Computationally, these SNPs were found to have no effect on the structure of FOXA2 protein. On the other hand, miRNA results showed that decreased expression of miR-124 was significantly HCC followed by cirrhotic groups versus control group in both sexes. It was additionally documented that reduction in miRNA-124 expression is more prominent in females than males (P < 0.05).Conclusion: These findings suggest that FOXA2 DBD alterations are not correlated with sexual dimorphism as protein structure is not affected. But, they may be correlated with HCC progression due to DNA repair disorders. On the other hand, miR-124 reduced expression has prognostic value in hepatocellular carcinoma and may serve as a possible prognostic marker for liver cancer.