Thus the present study was initiated to investigate whether miR-152 are aberrantly regulated by the HCV core protein, and involved in the regulation of the aberrant proliferation of HCV-HCC cells. Methods: MiR-152 levels were examined by stem-loop real-time RT-PCR (SLqRT-PCR).

Cell proliferation was analyzed by MTT and colony formation assay. Cell cycle analysis was performed by propidium iodide staining. A luciferase reporter assay was conducted to confirm miRAN-target association. Wnt1 expression was determined by real-time qPCR and Western blotting. Results: HCV core protein significantly suppressed miR-152 expression, and led to significant Wnt1 up-regulation with a concomitant aberrantly promoted proliferation. Moreover, we validated that

Carfilzomib miR-152 inhibition promoted, while miR-152 mimics inhibited cell proliferation. Using a luciferase activity assay, FQ-PCR and RXDX-106 purchase western blot, Wnt1 was identified as a target of miR-152 in HepG2 cells. Most notably, salvage expression of miR-152 after AdHCV core infection into the HepG2 cells for 24h almost totally reversed the proliferation-promoting effect of the HCV core protein, and meanwhile, reduced the expression of both Wnt1 mRNA and protein to basal levels. Conclusion: These findings provide important evidence that the reduced miR-152 expression by HCV core protein over-expression can lose an inhibitory effect on Wnt1, which might, at least partially lead to cell proliferation of liver cancer cells. MiR-152 may have a therapeutic potential to suppress liver cancer proliferation. Keywords: miR152; Wnt1; cell proliferation; cell cycle; HCV core Disclosures: The following people have nothing to disclose: Huang S. Feng, Yan Xie, Yang Ping, Chen Pu, Zhang L. Ping MicroRNAs (miRNAs) are evolutionary conserved small noncoding RNAs that post-transcriptionally regulate gene expression. Numerous studies have reported the key

role of miRNAs in development, cell proliferation, apoptosis, and tumor biology. However, the implication of miRNAs in liver development is not fully understood. check details By using an experimental model developed by our group that allows the induced and controlled differentiation of mouse fetal hepatoblasts (MFHs) into mature hepatocytes, we identified miR-148a as a hepatospecific miRNA highly expressed in adult liver. The main finding of our study revealed that miR-148a was critical for hepatic differentiation via the direct targeting of DNA methyltransferase (DNMT) 1, a major enzyme responsible for epigenetic silencing, thereby allowing the promotion of the “adult liver” phenotype. It was also confirmed that the reduction of DNMT1 by RNA interference significantly promoted the expression of the major hepatic biomarkers. In addition to the essential role of miR-148a in hepatocyte maturation, we identified its beneficial effect through the repression of hepatocellular carcinoma (HCC) cell malignancy.