Deregulation of miR-34a and Its Chaperon Hsp70 in Hepatitis C virus-Induced Liver Cirrhosis and Hepatocellular Carcinoma Patients

BACKGROUND: MicroRNA deregulation may occur during hepatocellular carcinoma (HCC) genesis and progression stages. MicroRNA-34a (miR-34a) functions as a tumor suppressor and is down-regulated or silenced in a variety of human cancers, while heat shock proteins (Hsps) play important roles in assisting protein folding and preventing both protein aggregation and transport across membranes. The present study aimed to evaluating serum expression of miR-34a and its target Hsp70 for early detection of HCC in patients with liver cirrhosis (LC), focusing on correlations with clinicopathological features. METHODS: A total of 180 patients were included: 120 with HCC on top of LC (60 with either early or late HCC) and 60 patients with HCV-related LC. In addition, 60 healthy individuals were considered as controls. Real-time polymerase chain reactions were performed for expression profiling of serum miR-34a and Hsp70 and for allelic discrimination of the promotor variant (rs2763979, C/T). In addition, in silico analysis was carried out. RESULTS: All participants were heterozygote for the promotor polymorphism. miR-34a serum levels were significantly under-expressed in LC and especially HCC patients as compared to controls. Associations with a high Child-Turcotte-Pugh (CTP) score, advanced cancer stage, and number of masses were noted. In contrast the target Hsp70 was significantly overexpressed in cancer patients but not in LC group and inversely correlated with miR-34a levels. CONCLUSION: Utility of circulating miRNAs as biomarkers for early detection of HCC was raised. Future large-scale studies are warranted to confirm the current findings.