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Abstract
Hepatocellular carcinoma (HCC) is one of the most highly lethal and malignant cancers of the world, it is the fifth most common cancer in men and ninth in women. HCC is sexually dimorphic in mammals, with males being much more likely to develop HCC than females. Molecular mechanism underlying this sexual dimorphism remains unclear. In this regards, forkhead box A (FOXA) transcription factors; namely FOXA1 and FOXA2 have shown to play a role in liver function and recruitment of estrogen and androgen receptors (ER-Ü and AR) to cis-regulatory elements. Recently, mutations of multiple FOXA2 binding sites have shown to cause impaired binding of FOXA2 and ER to their target genes, and ultimately alter target gene(s) expression in the women livers with HCC. On the other hand, miRNA is a class of non-coding RNAs that regulate various pathological and physiological processes by modulating their target mRNAs{u2019} expression, and some miRNA genes were found to be located in cancer-associated genomic regions, indicating that they are cancer-related and could be used as prognostic and diagnostic biomarkers as well as potential molecular targets. In the present investigation, we try to through some light upon the molecular mechanisms underlying HCC sexual dimorphism with special reference to Egyptian population. Our approach is to investigate FOXA2 DNA binding domain (DBD) mutations as well as miRNA-124 expression in both sexes. FOXA2 DNA binding region has been sequenced to identify any HCC-related single nucleotide polymorphism (SNP) that may impair FOXA2 binding to its target gene(s). Also miRNA-124 expression profile has been quantitatively assessed by real-time PCR to correlate its differential expression to HCC in view of sexual dimorphism