Crosstalk between liver-related microRNAs and Wnt/β-catenin pathway in hepatocellular carcinoma patients

• Published in: Arab journal of gastroenterology Vol. 18; no. 3; pp. 144 - 150
• Main Authors: Ashmawy, Abeer M., Elgeshy, Khaled M., Abdel Salam, El-Said T., Ghareeb, Mohamed, Kobaisi, Mohamed H., Amin, Hebat Allah A., Sharawy, Sabry K., Abdel Wahab, Abdel Hady A.
• Format: Journal Article
• Language: English
• Published: Egypt Elsevier B.V 01.09.2017
• Subjects: Adenomatous Polyposis Coli Protein - metabolism; Aged; beta Catenin - metabolism; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Case-Control Studies; Cyclin D1 - metabolism; Down-Regulation; Female; Gene Expression; Hepatitis C, Chronic - genetics; Hepatocellular carcinoma; Humans; Inhibitor of Apoptosis Proteins - metabolism; Liver Cirrhosis - genetics; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; microRNAs; MicroRNAs - genetics; Middle Aged; Neoplasm Grading; Proto-Oncogene Proteins c-myc - metabolism; Up-Regulation; Wnt Signaling Pathway; Wnt/β-catenin; microRNAs; Hepatocellular carcinoma; Wnt/β-catenin
• ISSN: 1687-1979; 2090-2387; 2090-2387
• DOI: 10.1016/j.ajg.2017.09.001

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with highest incidence in Asia and Africa. MicroRNAs (miRNAs), a class of non-coding single stranded RNA, which not only post transcriptionally regulate gene expression but also respond to signaling molecules to affect cell functions such as Wnt/β-catenin signaling specifically in HCC. The goal of this study is to investigate the crosstalk between Wnt/β-catenin signaling proteins and microRNAs expression in HCC patients. Fresh tissue samples of 30 primary HCC patients and 10 control subjects were included. Expression level of 13 different miRNAs (miR-10a- miR-106b- miR-99a- miR-148a- miR-125b- miR-30e- miR-183- miR-155- miR-199a- miR-199a3p- miR-24- miR-122 and miR-215) were examined using real-time PCR assay. Five proteins involved in the Wnt/β-catenin pathway (β-catenin, APC, c-myc, survivin and cyclin D1) were analysed by immunohistochemistry technique. The correlation between miRNAs expression levels with protein expressions was assessed. Up-regulation of miR-155 and miR-183 was reported in HCC patients compared to normal controls and this up-regulation was significantly correlated with liver cirrhosis in the case of miR-155 (p<0.05) referring to their oncogenic activity. Down-regulation was observed for 11 miRNAs in HCC indicating their tumour suppression activity. MiRNA-10a, miR-30e, miR-215, miR-125b and miR-148a were significantly correlated with the expression of important players in Wnt/β-catenin pathway including β-catenin, APC and c-myc (p<0.05). Detailed analysis revealed that miR-215 is associated with the grade of the disease and miR-125b is associated with HCV infection. Collectively, our data showed potential role of miR-10a, miR-30e, miR-215, miR-125b and miR-148a as important mediators in HCC progression. Furthermore, their association with Wnt/β-catenin cascade proteins could be exploited to develop new therapeutic target strategies in HCC.