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An Integrative Analysis of the Micro-Rnas Contributing in Stemness, Metastasis and B-Raf Pathways in Malignant Melanoma and Melanoma Stem Cell Publisher



Sahranavardfard P1 ; Madjd Z2 ; Razavi AE3 ; Ghanadan A3, 4 ; Firouzi J1 ; Khosravani P1 ; Ghavami S5, 6, 7, 8 ; Ebrahimie E9, 10 ; Ebrahimi M1
Authors
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Authors Affiliations
  1. 1. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  2. 2. Department of Pathology, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Iran National Tumor Bank, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Dermatopathology, Razi Skin Hospital, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Human Anatomy and Cell Sciences, University of Manitoba, Manitoba, Canada
  6. 6. Biology of Breathing, Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada
  7. 7. Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  8. 8. Research Institute in Oncology and Hematology, Cancer Care Manitoba, University of Manitoba, Winnipeg, Canada
  9. 9. School of Animal and Veterinary Sciences, The University of Adelaide, Adelaide, Australia
  10. 10. Genomics Research Platform, School of Life Sciences, College of Science, Health and Engineering, La Trobe University, Melbourne, Australia

Source: Cell Journal Published:2021


Abstract

Objective: Epithelial-mesenchymal transition (EMT) and the stemness potency in association with BRAF mutation are in dispensable to the progression of melanoma. Recently, microRNAs (miRNAs) have been introduced as the regulator of a multitude of oncogenic functions in most of tumors. Therefore identifying and interpreting the expression patterns of these miRNAs is essential. The present study sought to find common miRNAs regulating all three important pathways in melanoma development. Materials and Methods: In this experimental study, 18 miRNAs that importantly contribute to EMT and have a role in regulating self-renewal and the BRAF pathway were selected based on current literature and cross-analysis with available databases. Subsequently, their expression patterns were evaluated in 20 melanoma patients, normal tissues, serum from patients and control subjects, and melanospheres. Pattern discovery and integrative regulatory network analysis were used to find the most important miRNAs in melanoma progression. Results: Among 18 selected miRNAs, miR-205, -141, -203, -15b, and -9 were differentially expressed in tumor samples than normal tissues. Among them, miR-205, -15b, and -9 significantly expressed in serum samples and healthy donors. Attribute Weighting and decision trees (DT) analysis presented evidence that the combination of miR-205, -203, -9, and -15b can regulate self-renewal and EMT process, by affecting CDH1, CCND1, and VEGF expression. Conclusion: We suggested here that miR-205, -15b, -203, -9 pattern as the key miRNAs linked to melanoma status, the pluripotency, proliferation, and motility of malignant cells. However, further investigations are required to find the mechanisms underlying the combinatory effects of the above mentioned miRNAs. © 2021 Royan Institute (ACECR). All rights reserved.
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