MicroRNA-92a -mediated endothelial to mesenchymal transition controls vein graft neointimal lesion formation

PurposeLong-term failure of vein grafts due to neointimal hyperplasia remains an important problem in coronary artery bypass graft surgery. Endothelial to mesenchymal transition (EndMT) contributes to vein graft vascular remodeling. However, there is little study on microRNA-mediated EndMT contributions to neointimal formation in vein graft. We hypothesized that microRNA-92a (miR-92a) might play an important role in determining EndMT contributions to neointimal formation.MethodsmiR-92a and EndMT-related proteins detected by qRT-PCR and Western blot in vitro and in vivo. Adeno-associated virus 6 (AAV6) delivery gene therapy was used to inhibit neointimal formation in vivo. The intimal hyperplasia of vein grafts was measured by HE staining, the expression of EndMT-related protein in vein grafts was measured by immunofluorescence. Immunohistochemistry and luciferase assay were used to detect potential targets of miR-92a.ResultsThe expression of miR-92a was found to be upregulated in neointimal hyperplasic lesions after vein grafting. Using cultured human umbilical vein endothelial cells (HUVECs), we show that TGF-β1 treatment of HUVECs significantly increased miR-92a expression and induced EndMT, characterized by suppression of endothelial-specific markers (CD31 and VE-cadherin) and an increase in mesenchymal-specific markers (a-SMA and vimentin), while inhibition of miR-92a expression blunted EndMT in cultured HUVECs. Furthermore, AAV6 mediated miR-92a suppression gene therapy effectively resulted in decreased EndMT and less neointimal formation in vein grafts in vivo. We further identified that integrin alpha 5 (ITGA5) is a potential target gene involved in the development of neointima formation in these vein grafts.ConclusionThis data suggests that neointimal formation does not solely rely on vascular smooth muscle cell phenotypic switching but is also related to EndMT, and miR-92a-mediated EndMT is an important mechanism underlying neointimal formation in vein grafts.     

Challenges in cancer research and multifaceted approaches for cancer biomarker quest

Recent advances in cancer biology have subsequently led to the development of new molecularly targeted anti-cancer agents that can effectively hit cancer-related proteins and pathways. Despite better insight into genomic aberrations and diversity of cancer phenotypes, it is apparent that proteomics too deserves attention in cancer research. Currently, a wide range of proteomic technologies are being used in quest for new cancer biomarkers with effective use. These, together with newer technologies such as multiplex assays could significantly contribute to the discovery and development of selective and specific cancer biomarkers with diagnostic or prognostic values for monitoring the disease state. This review attempts to illustrate recent advances in the field of cancer biomarkers and multifaceted approaches undertaken in combating cancer.     

Emerging Molecular Strategies for Improving Rice Drought Tolerance

Rice occupies a pre-eminent position as a food crop in the world. Its production, how- ever, entails up to 3000 liters of water per kilogram of grain produced. Such high demand makes rice prone to drought easily. Sustainable rice cultivation with limited water resources requires the deployment of a suitable strategy for better water use efficiency and improved drought tolerance. Several drought-related genes have been evaluated in rice for their mode of action in conferring drought tolerance. Manipulation of components of abscisic acid signal transduction, stomatal density, deposition of cuticular wax, and protein modification pathways are emerging as priority targets. Gene reprogramming by microRNAs is also being explored to achieve drought tolerance. Genetically dissected Quantitative Trait Loci (QTLs) and their constituent genes are being deployed to develop drought-tolerant rice varieties. Progressive research and challenges include a better understanding of crucial components of drought response and search for new targets and the deployment of improved varieties in the field.     

Endogenous transcripts direct microRNA degradation in Drosophila,and this targeted degradation is required for proper embryonic development

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