Figure 1.
A schematic view of the chemo-resistance mechanisms induced by miRNAs. Drug efflux: Expression of P-glycoprotein (MDR1) is regulated through the binding of microRNAs (miR27a, miR-130, miR145, miR-298, miR-451) to their target mRNA. The microRNA (miR-145) three-dimensional mature structure was modeled using the Web Server RNAComposer [Popenda et al., 2012]. The atomic structure of the human mitochondrial ABC transporter ABCB10 [Shintre et al., 2013; PDB code 3ZDQ] is represented in ribbons using the program Chimera [Pettersen et al., 2004]. Drug metabolism: Using the same software described above, the action of miR-27a on dihydropyrimidine dehydrogenase [Dobritzsch et al., 2001; PDB code 1H7X], a major determinant of the pharmacokinetics of the anti-cancer drug 5-Fluorouracil, is reported. DNA methylation: Gene methylation by DNA methyltransferases is regulated by miR-29. In this panel, the atomic structure of the protein structure of mouse DNMT1 and a fragment of hemi-methylated CpG DNA [Song et al., 2012; PDB code 4DA4]. DNA excision repair: The figure shows the 3D structure of the central domain of human ERCC1, a DNA excision repair protein [Tsodikov, 2005; PDB code 2A1I] that is regulated by miR-139 and miR-199. DNA mismatch repair: miR-21 and miR-155 are involved in the regulation of the DNA mismatch repair protein MutS [Oblomova et al., 2000; PDB code 1EWR]. Intrinsic apoptosis: Bcl-2 three-dimensional structure [Checco et al., 2015; PDB code 5AGW] and the regulators miR-138 and miR-192 are shown. p53-mediated apoptosis: The quaternary assembly of the p53 protein core domains bound to a naturally occurring response element (RE) located at the promoter of the Bcl-2-associated X protein (BAX) gene [Chen et al., 2013; PDB code 4HJE].