Eradication of cancer stem cells through micrornas: a conceptual view
,1 Mohammad mahdi forghanifard
,2 Mohammad reza abbaszadegan
1. Medical Genetics Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2. Department of Biology, Damghan Branch, Islamic Azad University, Iran
3. Medical Genetics Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Micrornas (mirnas), as 19-24 nucleotides endogenous non-coding rnas, are involved in the most cellular processes playing a critical regulatory role in transcriptome content through post- transcriptional control of their target genes expression. cancer stem cells (cscs) are a small subpopulation of cells within the tumors which are generated during the normal differentiation process of somatic cells possessing the ability of self-renewal and tumorigenicity in vivo. therefore, we aimed to review the involved micrornas in maintenance of cscs self- renewal and pluripotency.
Analysis of mir-seq data and investigating through available databases including miratarbase, mirbase,mirpath, miranda,dianatools indicates the possible targets of mir-2oo, mir-302 and mir- 396.based on reported data of recent studies implication of micrornas contributing in cell reprogramming as a result of previous studies would be a possible way to induce the maintenance of self-renewal ability in the cancer stem cells.
While mir- 369 is capable to reprogram cellular metabolism in cancer cells, mir-200s blocks epithelial mesenchymal transition (emt) to repress invasion and metastasis of tumor cells, and mir-302 represses the expression of transmembrane transporter protein involved in multidrug resistance within reprogrammed cells, to increased chemo-resistance activity.
Key transcription factors such as oct4/sox2/klf4/myc (oskm), can establish stemness state in tumors leading to csc maintenance. since specific micrornas are involved in regulation of pluripotency and reprogramming of differentiated cells, one of the possible strategies used for cscs eradication would be mirna therapy to reduce cellular reprogramming. based on increasing evidence the combination of three micrornas including mir200s, mir302, and mir369 can induce pluripotent stem cells. henceforth, microrna targeting of reprogrammed cancer stem cells may decrease cscs initiating capacity and increase the sensitivity of tumor cells to chemotherapy.
Microrna, cancer stem cell, reprogramming, self-renewal ability, mirna therapy