Abstract

Myocardial infarction is the leading cause of death globally and lack of pristine early detectors drove us in search of novel biomarkers .MicroRNAs (miRs) are endogenous and evolutionarily conserved small non-coding RNAs (sncRNAs) (size 19–24 nt) that have been proven to be important post-transcriptional silencers of gene expression through sequence-specific base pairing with the 3’UTR of the target messenger RNAs (miRNAs) transcript. Thus it either  degrade or enhances protein translation. miRNAs have the capacity to influence both physiological and pathological cellular processes by involving in cell differentiation, cell growth, apoptosis, angiogenesis and inflammation. Transcriptomics  is the study of how our genes are regulated and expressed in different biological settings. Technical advances now enable quantitative assessment of all expressed genes (i.e. the entire ‘transcriptome’) in a given tissue at a given time. These approaches provide a powerful tool for understanding complex biological systems and for developing novel biomarkers

We have done  a globlal transcriptome profiling of miRNAs in  physiological hypertrophied Rat heart. We also reported down-regulation of miR-99 family in a2m-induced physiological hypertrophy. Subsequently, qRT-PCR and western blot analysis revealed Early growth response gene-1 (Egr-1) mediated up-regulation of miR-99 negatively regulates Akt signalling in isoproterenol-induced pathological hypertrophy in H9c2 cardiomyocytes. Also, ChIP-PCR (Chromatin immuno precipitation-PCR) of rat genome confirmed the binding of Egr-1 at miR-99 promoter.  Thus, Egr-1 mediated regulation of miR-99 family plays an important role in determining the pathophysiology of cardiac hypertrophy. Hypertrophy is established as highest prevailing risk factor for myocardial infarction and hypertrophied heart can be an indicator of failing heart. Since miRNAs are found to be stable in circulation, detection of miR-99 level in serum gives profound insight into pathological state of heart. Serum analysis of myocardial infracted patients against healthy controls revealed significant elevation of miR-99b. Thus, this study suggests the potency of using circulating miR-99b as a novel diagnostic marker for myocardial infarction.  Yet another class of ncRNAs, PIWI-interacting RNAs (piRNAs) has fundamentally changed our understanding of post transcriptional regulation of transposons and other genes. Unlike miRNA and siRNA, the piRNAs are the most abundant but least studied RNA species in mammals. We identified an abundant and altered expression of piRNAs during cardiac hypertrophy. The differentially expressed piRNAs were validated by qRT-PCR. The detection of specific piRNA in serum of myocardial infarction patients suggests the potential of piRNA for diagnosis. Our findings provide a rationale for understanding the piRNA-retrotransposon interactions in cardiac system. Further, our present perspectives are to understand the mechanism, of circRNAs-miRNAs interactions towards pathogenesis of cardiac hypertrophy and heart failure.