Journal of Biotechnology & Biomaterials
Open Access

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level via degradation or translational inhibition of their target mRNAs. About one-thousand miRNAs have been identified and sequenced in humans, and the number of miRNA genes is estimated at more than that number. Individual miRNA is functionally important as a transcription factor because it has the ability to regulate the expression of multiple genes through binding to its target with imperfect and/or perfect complement. A big amount of diseases in which dysregulation of miRNAs has been implicated is constantly growing. Compared with others, far less is known about the role of miRNAs in diabetes and its complications. Several miRNAs have been identified as having a physiological role in tissues in which diabetes complications occur. Whether these miRNAs are involved in the damage that occurs in diabetes is yet to be established. The association between altered miRNA expression and the development and progression of the various diabetes complications implicates certain miRNAs in the development of diabetes-related injury in the heart. Accordingly, altered miRNA expressions have been reported during hypoxia in the heart. Therefore, these newly discovered small molecules are attracting attention of research area as possible new drug targets for use in the therapy of different types of cardiac dysorders.MicroRNA-profiling was performed in freshly isolated left ventriclular cells from diabetic rats. Using microarray analysis, we identified marked changes in the expression of 43 miRNAs (37 of them were downregulated while 6 miRNAs were upregulated) out of examined total of 351 miRNAs. Among them, 6 miRNAs were further validated by real-time PCR. The expression levels of miR-1, miR-499, miR-133a, and miR-133b were markedly depressed in the diabetic cardiomyocytes while miR-21 level increased and miR-16 level unchanged. Since changes in the level of muscle-specific miR-1 has been implicated in cardiac diseases and its specific molecular targets involved in its action, we first examined the protein levels of some SR-associated proteins such as junctin and triadin. Junctin but not triadin is markedly overexpressed in diabetic cardiomyocytes. Luciferase reporter assay showed that junctin is targetted by miR-1. Taken together, our data demonstrates that control the levels of some miRNAs including miR-1 and its target protein junctin is an important tool for the development of diabetic cardiomyopathy. Our recent data, performed to examine the effects of chronic hypoxia on the regulation of microRNAs and their potential target protein expressions in HL-1 cells after 48 hours of hypoxia exposure, among a total of 275 miRNAs, 24 miRNAs were significantly downregulated and 9 miRNAs were upregulated. Hypoxia also significantly upregulated GADPH and downregulated beta-2-microglobulin protein levels. Furthermore, miRNA target protein interaction in silico analyses identified 3? UTR region of GADPH mRNA as a direct miR-188 potential target, which is downregulated by hypoxia. Similarly, our present study showed that hypoxia- induced upregulated miR-212 is a potential target for β-2-microglobulin 3? UTR. Therefore, it is clearly tempting to speculate that the innovative miRNA-interference technologies developed lately for manipulating the action of miRNAs by interfering with their expression, stability, and function as new approaches for miRNA research, and gene therapy will be introduced in the therapy of heart diseases as well as the identification of the differences in heart function due to different types of pathologies.

Biography

Belma Turan is a professor at Department of Biophysics, Faculty of Medicine, Ankara University, Turkey. She completed her PhD in Biophysics, Ankara University (Ankara, 1982). She was elected as a principal member of International Academy of Cardiovascular Sciences, 2005. She was a Visiting Professor, Manitoba University Institute of Cardiovascular Sciences (Canada), 2003. She has published 1 book and 9 book chapters, 83 research publications in journals (Covered by Science Citation Index) and 59 publications in conferences (Covered by Science Citation Index, 24 peer reviewed journal publications, 39 invited presentations and 159 other presentations.