Role Of MicroRNA-223 And Its Target Gene Oncogene C-myc In Hepatocellular Carcinoma Pathogenesis

Objective Over-expression of oncogene c-myc is key to hepatocarcinogenesis. Here, regulatory role of microRNA-223(miR-223) on c-myc and their role in hepatocarcinogenesis are investigated.Method miR-223 and c-myc mRNA expression in normal, paraneoplastic, liver cancer tissues and liver cancer cells were tested with microRNA microarray, quantitative real-time PCR (qRT-PCR), c-myc protein expression was detected by Western blot. miR-223 mimic was transfected into Hep G2 and expression changes of c-myc mRNA and protein were measured with qRT-PCR and Western blot respectively.Results miR-223 was down-regulated (relative expression 0.055±0.015,0.030±0.008 and 0.020±0.016 respectively, down-regulated 30.77% and 61.53% respectively) in adjacent and hepatocellular carcinoma tissues compared to normal liver tissues, expression of miR-223 was also decreased (relative expression 0.011±0.006 and 0.005±0.003 respectively , P <0.05) in HepG2 cell compared to fetal liver cells L02; Expression of c-myc mRNA and protein increased (mRNA relative expression 0.029±0.023,0.136±0.071 and 0.425±0.026 respectively,P<0.05; protein relative expression 0.137±0.015,0.299±0.033 and 0.439±0.027 respectively, P <0.05) in paraneoplastic and HCC tissues compared with normal liver tissues. It prompts that the expressions of miR-223 and c-myc are negative correlated direction. There is no obvious difference of c-myc mRNA expressions(relative expression 0.031±0.009,0.032±0.007 and 0.056±0.029 respectively, P>0.05)after miR-223 mimics transfection by HepG2, and c-myc protein expression was down-regulated significantly ( relative expression 0.423±0.041,0.116±0.015 and 0.432±0.034 respectively, P<0.05).Conclusions The expression of miR-223 was lower in adjacent liver tissues and hepatic carcinoma tissues than that in normal liver tissues , and also lower in Hep G2 liver cancer cells than that in infetal liver cells L02, it prompts the abnormal expression of miR-223 occurs in the liver cancer.; The miR-223 in up-regulated c-myc gene expression and oncogenic activity participates in the regulation of liver cancer; and the up-regulated miR-223 in liver cancer cells can decrease the expression of c-myc gene expression and biological activity, it prompts miR- 223 involved in c-myc pathway in the carcinogenic mechanism. Due to the miR-223 expression down-regulated in hepatocellular to cause the loss of inhibition to c-myc expression, the c-myc abnormal high-expression may play a dynamic role in Hepatocarcinogenesis. It prompts the increased expression of miR-223 could be a potentially valuable method of prevention and treatment of liver cancer.