Mitochondrial damage mediated by miR-1 overexpression in cancer stem cell

Abstract It is well known that cells rely on mitochondrial respiration for survival. However, the effect of microRNAs (miRNAs) on mitochondria of cells has not been extensively explored. Our results indicated that the overexpression of an miRNA (miR-1) could destroy mitochondria of cancer stem cells. MiR-1 was downregulated in melanoma and breast cancer stem cells (MSCs and BCSCs) compared with cancer non-stem cells. However, the upregulation of miR-1 in cancer non-stem cells did not induce mitochondrial damage. The miR-1 overexpression caused mitochondrial damage of cancer stem cells by directly targeting the 3’ untranslated regions (3’UTRs) of MINOS1 (mitochondrial inner membrane organizing system 1) and GPD2 (glycerol-3-phosphate dehydrogenase 2) genes and interacting with LRPPRC protein (leucine-rich pentatricopeptide-repeat containing protein), a protein localized in mitochondria. MINOS1, GPD2 and LRPPRC in mitochondria were required for mitochondrial inner membrane. The results of in vitro and in vivo assays demonstrated that the miR-1 overexpression induced mitophagy of cancer stem cells. Therefore, our study contributed novel insights into the mechanism of miRNA-mediated regulation of mitochondria morphology of cancer stem cells.