Post-transcriptional gene-expression regulation by micro RNA (miRNA) network in renal disease ☆ Tamás Kaucsár 1 , Zsuzsanna Rácz 1 , Péter Hamar ⁎ Semmelweis University, Institute of Pathophysiology, H-1089, Budapest Nagyvárad t. 4, Hungary abstract article info Article history: Received 26 April 2010 Accepted 1 October 2010 Available online 19 October 2010 Keywords: miRNA Gene-expression Renal disease In vivo Micro RNAs (miRNAs) are a recently discovered class of small, non-coding RNAs with the function of post- transcriptional gene expression regulation. MiRNAs may function in networks, forming a complex relationship with diseases. Alterations of specific miRNA levels have significant correlation with diseases of divergent origin, such as diabetic or ischemic organ injury including nephropathy, and malignant diseases including renal tumors. After identification of disease-associated miRNAs, there are two options of influencing their tissue expression. The function of miRNAs can be inhibited by antisense oligonucleotides (ASOs), which have been shown to silence specific miRNAs in vivo. Moreover, miRNA activity can be also mimicked or enhanced by delivering chemically synthesized miRNAs. Thus, modifying the expression of miRNAs is a potential future gene-therapeutic tool to influence posttranscriptional regulation of multiple genes in a single therapy. In this review we focus on key renal miRNAs with the aim of revealing the pathomechanisms of renal diseases. Nucleic acid therapy with oligonucleotides and short interfering RNA (siRNA) are under clinical evaluation presently. Similar therapeutic strategies, to influence miRNA function is also already under clinical investigation in RNA interference trials. We summarize here studies specifically aimed at the modification of miRNA expression. Research on the post-transcriptional regulation of gene expression by miRNA may reshape our understanding of renal pathophysiology and consequently may bring new diagnostic markers and therapeutic agents. © 2010 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1391 1.1. Micro RNAs (miRNAs): generation and mechanism of action (Fig. 1) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1391 1.2. MiRNA nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1391 1.3. MiRNA function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1391 1.4. Influencing miRNA expression in vivo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1392 1.5. Nucleic acid therapy — problems and solutions of delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1392 1.6. Inhibition of miRNA function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1392 1.6.1. Chemical modification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1393 1.6.2. Locked nucleic acids (LNAs) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1394 1.6.3. AMOs function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1394 1.7. Enhancement of miRNA function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1394 1.7.1. Delivery of shRNA coding vectors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1394 1.8. Kidney specific miRNAome, renal disease specific alterations, and functional investigations of miRNAs in the kidney. . . . . . . . . 1394 1.9. Diagnostic utilization of miRNAs: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1396 1.10. Non-renal applications: further functional investigations of miRNAs in vivo . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1396 2. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1399 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1399 Advanced Drug Delivery Reviews 62 (2010) 1390–1401 ☆ This review is part of the Advanced Drug Delivery Reviews theme issue on “Drug Targeting to the Kidney”. ⁎ Corresponding author. E-mail address: hampet@net.sote.hu (P. Hamar). 1 The 2 authors: TK and Zs R contributed equally. 0169-409X/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.addr.2010.10.003 Contents lists available at ScienceDirect Advanced Drug Delivery Reviews journal homepage: www.elsevier.com/locate/addr