An Update on MicrornaÃ¢ÂÂs and Metabolic Regulation with Future TherapeuticPotentials Regarding Diagnosis and Treatment of Obesity, MetabolicSyndrome and Other Related Disorders

Micro RNAs is a family of highly conserved, single stranded 1923 nucleotide long noncoding endogenous RNAs which negatively regulate gene expression, either by inhibiting translation or by degrading largest mRNAs [1]. Over 2000 unique miRNAs have been identified in humans [2] The miRNAs are initially transcribed as long RNA precursors termed primary miRNAs (pri-miRNAs) that require the RNAse III enzyme Drosha in the nucleus to trim them into premiRNAs The premiRNAs are characterized by a stemloop or hairpin structure of 70-100 nucleotides and are exported to the cytoplasm by the nuclear export factor exportin 5. The pre-miRNAs are subsequently cropped to become mature miRNA by another RNAse enzyme Dicer in the cytoplasm [3]. Although our understanding of the specific roles of miRNAs in cellular function is only beginning, recent studies revealed that miRNAs play a pivotal role in the most critical biological events such as development, proliferation, differentiation, apoptosis, transductionand carcinogenesis [4]. The mature miRNA’s are conserved about 2 nucleotides noncoding RNAs that anneal to inexactly complementary sequences in the 3’untranslated regions(3’UTR) of target mRNA of protein coding genes, resulting in silencing of the target gene.While the mechanism of action of miRNAs is yet to be fully understood , the widely known mode of gene regulation by miRNAs occurs at the post transcriptional level by either specific inhibition of translation or induction of mRNACleavage [5,6], resulting in a reduction in protein levels of their targets (Figure1) [7]. Alternatively, if the expression of miRNA’s is inhibited, then increased protein expression may be seen in animal species. miRNAs are also capable of modifying chromatin (Figure1) [6]. dsRNA miRNA complex which is composed of the mature miR and its passenger strand (miR”) is unwound by helicase activities of the Argonaute (Ago) multiprotein complex, globally known as the RNA-induced silencing complex (RISC) [8-10]. Determination of the active (guide) strandis based upon simple energetics between strands at the 5’ ends of the dsRNA complex [11]. The preferred guide strand is subsequently incorporated into the RISC complex by directly binding to the key component of Ago [12]. miRNA target sites generally occur within the reading frame of and in 5’ UTR [13]. We can regulate cancer, obesity and viral induced diseases by using miR. Further work is going on in developing of potential RNAi (miRNAand siRNA) molecules to get insights for the chemical synthesis of antiviral RNA molecule for the treatment of middle east respiratory syndrome (MERS) corona virus (CV), at genomic level [14], or development of antiviral RNA molecule for the treatment of Merkel cell polymyxoma virus (MCV) which causes 80% Merkel cell carcinomas (MCC), for T antigen silencing at genome level [15]. Similarly in HSV-1, siRNA were designed against ICP22 (US1) gene (intermediate gene) responsible for genomic replication of HSV. This approach may help us in synthesizing antiviral RNA molecules for treatment of HSV-1, at genomic level [16]. Zhou et al. have further reviewed the role of nanoparticle based delivery of RNA interference (RNAi) therapeutics [17] along with different delivery systems for various cancers e.g. role of (ALN-VSP), a lipid formation delivering siRNAs against two important cancer genes, kinesin spindle protein (KSP) and vascular endothelial growth factor (VEGF), for the treatment of liver cancers in phase 1 trials [18]. Further doxorubicin combined with polyethylenimine (PEI) along with Pin X1-si RNA is delivered to knockout PIN2 interacting protein (PINX1) gene in C6 glioma cells. Pin X1 is anucleolar protein associated with telomere and telomerase. Thus Pin X1-siRNA-mPEG (monomethoxy poly ethyleneglycol)-PEIsuper paramagnetic ironoxide nanoparticles (SPION) in combination with doxorubicin maybe a more effective treatment of gliomas with negligible side effects [19]. Similarly ScFv decorated Poly ethylene glycol (PEG)-block poly D,L-Lactide (PLA)-based nanoparticles show greater potential for targeted RNAi therapy of Her2(+) breast cancer [20].