MicroRNA­125a­mediated regulation of the mevalonate signaling pathway contributes to high glucose­induced proliferation and migration of vascular smooth muscle cells.

Hyperglycemia contributes to the excessive proliferation and migration of vascular smooth muscle cells (VSMC), which are closely associated with atherosclerosis. MicroRNAs (miRNAs/miRs) constitute a novel class of gene regulators, which have important roles in various pathological conditions. The aim of the present study was to identify miRNAs involved in the high glucose (HG)­induced VSMC phenotype switch, and to investigate the underlying mechanism. miRNA sequencing and reverse transcription­quantitative PCR results indicated that inhibition of miR­125a expression increased the migration and proliferation of VSMCs following HG exposure, whereas the overexpression of miR­125a abrogated this effect. Furthermore, dual­luciferase reporter assay results identified that 3­hydroxy­3-methyglutaryl­coA reductase (HMGCR), one of the key enzymes in the mevalonate signaling pathway, is a target of miR­125a. Moreover, HMGCR knockdown, similarly to miR­125a overexpression, suppressed HG­induced VSMC proliferation and migration. These results were consistent with those from the miRNA target prediction programs. Using a rat model of streptozotocin­induced diabetes mellitus, it was demonstrated that miR­125a expression was gradually downregulated, and that the expressions of key enzymes in the mevalonate signaling pathway in the aortic media were dysregulated after several weeks. In addition, it was found that HG­induced excessive activation of the mevalonate signaling pathway in VSMCs was suppressed following transfection with a miR­125a mimic. Therefore, the present results suggest that decreased miR­125a expression contributed to HG­induced VSMC proliferation and migration via the upregulation of HMGCR expression. Thus, miR­125a­mediated regulation of the mevalonate signaling pathway may be associated with atherosclerosis.

[Research advances on treatment of hepatitis C infection based on RNA interference and microRNA modulation].

Infection with hepatitis C virus (HCV) is one of the major global health problems, approximately 170 million people are infected worldwide. The chronic HCV infection is associated with a high risk of developing liver cirrhosis, hepatocellular carcinoma (HCC) and liver failure. Unfortunately, there is still no effective vaccine or antibodies available for the prevention of infection. RNA interference (RNAi) represents a promising new approach to combat viral infections, and recent developments in the field of gene therapy have increased the feasibility of clinical applications. RNAi techniques have made rapid progress in the basic understanding of HCV biology and revealed numerous new viral and host-cell factors as potential targets for therapy. Together with the improvement of gene delivery technique and the discovery of the critical role of microRNA (miRNA) in HCV infection, RNAi and miRNA-based antiviral strategies hold great promise for the future. In this article, we provide a comprehensive overview of current developments of therapeutic targets of RNAi, liver-targeted delivery systems and the potential applications of miRNAs in treatment of hepatitis C infection.