Dissecting microrna- mediated reprogramming of cancer stem cells: a conceptual view

Endogenous non-coding RNAs containing 19-24 nucleotides are defined as microRNAs and considered as major post-transcriptional regulatory determinants of most cellular processes. Duringtumorigenesis through normal differentiation process of somatic cells, generation of small subpopulation within tumors take place as cancer stem cells (CSCs). This subpopulation of tumor resembles some critical characteristics of embryonic stem cells (ESCs) such as unlimited self-renewal activity, multi-lineage differentiation, and maintenance of the stemness state in vivo. Indeed, it is phenotypically similar to undifferentiated ESCs. OCT4/SOX2/KLF4/MYC (OSKM), as pluripotency key transcription factors, have an obvious impact on tumorigenesis. Intriguingly, overexpression of OSKM factors resulted in the transformation of somatic cells to induced pluripotent cancer stem cells (iPCSCs), fully reprogrammed cells in various tissue types, as well as cancer development. microRNAmediated reprogramming of OSKM factors in OSKM-induced tumors would primarily lead into epigenetic modifications and reprogramming of differentiated cells to pluripotent stem cells. Evidently, a combination of some microRNAs (such as miR-200s, miR-302, and miR-367) induce pluripotent stem cells. miR-302 regulates the expression of the pluripotency markers (OCT4, SOX2, NANOG, and SSEA-3/4), represses the expression of transmembrane transporter protein involved in multidrug resistance within reprogrammed cells, and stimulates somatic cell reprogramming resulted in the generation of iPCSCs through DNA demethylation. While miR-302 facilitates mesenchymal-epithelial transition (MET, the reverse process of EMT), miR-200s blocks epithelial-mesenchymal transition (EMT) and represses the invasion and metastasis of tumor cells. Henceforth, microRNA-mediated reprogramming of CSCs decreases their initiating capacity and increases the sensitivity of tumor cells to chemotherapy. This corroborates a great relevance for future diagnostic and therapeutic approaches through targeting either pluripotency factors or CSCs as the supposed root of the tumor

کلیدواژه ها:

Cancer Stem Cells ، Stem Cells and Cancer ، Cancer Genetics ، Cancer Treatment and Management ، Targeted Cancer Therapy