Lettlova 2015 Abstract MiP2015
|Role of the microRNA-301a in the regulation of mitochondrial function in cancer cells.|
MicroRNAs (miRNAs) are 22 nucleotides long, single stranded, non-coding RNAs that negatively regulate gene expression by binding to mRNA, resulting in translation inhibition or mRNA degradation. MiRNAs regulate a wide range of cellular functions, and their abnormal expression is linked with many pathological conditions including cancer. New findings indicate that miRNAs play also an important role in the regulation of mitochondrial function and biogenesis.
MiRNA-301a is an oncogenic miRNA whose expression is associated with tumour development, metastases and overall poor prognosis. MiR-301a as a putative mitochondrial regulator was identified by the analysis of miRNAs expression profile in cells treated with mitochondrially targeted α-tocopheryl succinate (MitoVES), a compound that concentrates in mitochondria, induces profound generation of ROS leading to dysfunction of mitochondria. Treatment with MitoVES caused a significant downregulation of miR-301a compared to control cells.
Web-based miRNA related databases (MiRWalk, microRNA.org,miRBase) identified that genes connected with mitochondrial function, such as PPARGC1A, ESR1 and PPARG, possess a putative miR301a-binding seed sequence in their mRNA. We have observed a decrease in the expression of PPARGC1A, ESR1 and PPARG in MCF7 cells overexpressing inducible miRNA-301a after addition of doxycycline. Additionally, we detected differences in the expression of genes regulated by ESR1 and PGC1α such as TTF1A and GREB1A. Importantly, we have found markedly elevated levels of miR-301a in tumour spheres generated in vitro that exhibit properties of cancer stem cells in comparison with their normal counterparts.
In summary, we propose that miR-301a plays a role in the regulation of mitochondrial function and biogenesis, describing a novel, so far unknown role of miR301a in mitochondrial biology. Since high expression of miR-301a is associated with higher metastatic potential and poor prognosis, identification of the role of miR-301a in the regulation of mitochondrial function could also shed more light on the role of mitochondria in cancer progression.
Labels: MiParea: mt-Biogenesis;mt-density, mtDNA;mt-genetics, Pharmacology;toxicology, mt-Awareness Pathology: Cancer Stress:Oxidative stress;RONS
Event: A2, Poster MiP2015
1-Acad Sc of the Czech Republic, Inst Biotechnology, Prague, Czech Republic; 2-Griffith Univ, Southport, Queensland, Australia; 3-Fac Sc, Charles Univ Prague, Czech Republic. -