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MicroRNA-203 reinforces stemness properties in melanoma and augments tumorigenesis in vivo
Authors:Parisa Sahranavardfard  Javad Firouzi  Masoumeh Azimi  Pardis Khosravani  Raheleh Heydari  Amirnader Emami Razavi  Mahshad Dorraj  Faezeh Keighobadi  Marzieh Ebrahimi
Affiliation:1. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;2. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran;3. Iran National Tumor Bank, The cancer institute of Iran, Tehran University of Medical Sciences, Tehran, Iran

Abstract:One of the challenges encountered in microRNA (miRNA) studies is to observe their dual role in different conditions and cells. This leads to a tougher prediction of their behavior as gene expression regulators. miR-203 has been identified to play a negative role in the progression of malignant melanoma; however, it has been reported, with dual effect, as both an oncomiR and tumor suppressor miRNA in some malignancies, such as breast cancer, meanwhile, the role of miR-203 in melanoma stem cells or even metastatic cells is unclear. In the present study, after observation of upregulation of miR-203 in melanoma patient's serum and also melanospheres as cancer stem cells model, we examined its overexpression on the stemness potential and migration ability of melanoma cells. Our data demonstrated that the increased miR-203 level was significantly associated with significant increase in the ability of proliferation, colony and spheres formation, migration, and tumorigenesis in A375 and NA8 cells. All of these changes were associated with enhancement of BRAF, several epithelial to mesenchymal transition factors, and stemness genes. In conclusion, our results clearly determined that miR-203 could be down-regulateddownregulated in melanoma tissues but be overexpressed in melanoma stem cells. It has an important role as oncomiR and promote repopulation, tumorigenicity, self-renewal, and migration. Therefore, we suggested overexpression of miR-203 as biomarker for early detection of metastasis. However, more studies are needed to validate our data.
Keywords:melanoma stem cell  microRNA  miR-203  self-renewal  tumorigenesis
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