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microRNA Microarray Service - Application Note |
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microRNA profiling enables study of epigenetic mechanismsMicro RNAs (miRNAs) are small non-protein-coding RNA molecules that function as negative regulators of gene expression by base pairing with specific mRNAs. This either inhibits translation or promotes mRNA degradation. While their crucial function in regulation of genes involved in the control of development, cell proliferation, apoptosis, and stress response is well established, much less is known about their role in carcinogenesis. Significantly altered miRNA levels were observed in full-fledged tumors but specifically at the early pre-cancerous stage little data are available. Two recent publications by researchers from the Department of Biological Sciences at the University of Lethbridge give important new insight. The methodological foundation of both publications is the same two step approach: First, miRNA microarray expression analysis using LC Sciences µParaflo®technology is used as a fast, convenient, and cost-effective way to identify the differentially expressed miRNA genes. These results are then independently validated in the second step by qRT-PCR. In both research studies all qRT-PCRs confirmed data obtained by microarray analysis. “Induction of microRNAome deregulation in rat liver by long-term tamoxifen exposure” Pogribny et al. looked at the effect of tamoxifen (a known hepatocarcinogen) exposure on rats. The study shows substantial changes in the expression of miRNA genes in the liver over the time course of exposure (24 weeks). Specifically, deregulation of miRNA genes and their targets involved in cell cycle, DNA replication, chromatin maintenance, and apoptosis was observed. Expression of miRNA-targeted genes was monitored with Western immunoblotting. Up-regulated genes include known oncogenic miRNAs, such as the 17-92 cluster, miR-106a and miR-34 which corresponds to previously reported alterations in full-fledged tumors, including hepatocellular carcinomas. Noteworthy is the fact that the study indicates miRNA changes occurring prior to tumor formation and not solely as a consequence of a transformed state, thus opening the potential use of miRNAs as biomarkers for carcinogenic process. “Role of Epigenetic Effectors in Maintenance of the Long-term Persistent Bystander Effect in Spleen in vivo” Prof. Kovalchuk’s group presents the first study showing altered levels of miRNA in the plasma upon radiation exposure suggesting a role of miRNA is bystander effects. Specifically, altered levels of miR-194 in spleen and plasma of whole-body and head exposed animals were observed. Up-regulation of miR-194 in the exposed and bystander tissue was correlated with the down-regulation of its putative targets – de novo methyltransferase DNMT3a and methyl-binding protein MeCP2. Lowered levels of these proteins were linked to the significant global and LINE1 locus-specific hypomethylation, thus contributing to the genome destabilization and possibly further carcinogenesis. This report is the first study presenting evidence that radiation, in doses comparable to that currently used for clinical brain tumor treatment, induces long-term persistent bystander effects in rat spleen. About µParaflo®technology- The µParaflo®technology is a microfluidic platform for microarray biochips and biosensors. High quality custom DNA and RNA oligonucleotides as well as peptides and peptidomimetics can be synthesized in massive parallel in picoliter-scale reaction chambers (µParaflo® chips). About LC Sciences - LC Sciences offers specialty microarray services for nucleic acid/protein profiling and functional analysis, biomarker-discovery, and novel drug screening. More information about LC Sciences and the µParaflo®technology is available at: http://www.lcsciences.com.
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