An Integrative Analysis of The Micro-RNAs Contributing in Stemness, Metastasis and B-Raf Pathways in Malignant Melanoma and Melanoma Stem Cell

(Pages: 261-272)
Parisa Sahranavardfard, Ph.D., 1Zahra Madjd, M.D., Ph.D., 2Amirnader Emami Razavi, M.D., 3Alireza Ghanadan, M.D., 3,4Javad Firouzi, M.Sc., 1Pardis Khosravani, M.Sc., 1Saeid Ghavami, Ph.D., 5,6,7,8,*Esmaeil Ebrahimie, Ph.D., 9,10,*Marzieh Ebrahimi, Ph.D., 1,*
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Department of Pathology, Iran University of Medical Sciences, Tehran, Iran
Iran National Tumor Bank, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
Department of Dermatopathology, Razi Skin Hospital, Tehran University of Medical Sciences, Tehran, Iran
Department of Human Anatomy and Cell Sciences, University of Manitoba, Manitoba, Canada
Biology of Breathing, Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada
Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Research Institute in Oncology and Hematology, Cancer Care Manitoba, University of Manitoba, Winnipeg, Canada
School of Animal and Veterinary Sciences, The University of Adelaide, Adelaide, Australia
Genomics Research Platform, School of Life Sciences, College of Science, Health and Engineering, La Trobe University, Melbourne, Australia
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Department of Pathology, Iran University of Medical Sciences, Tehran, Iran
Iran National Tumor Bank, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
Department of Dermatopathology, Razi Skin Hospital, Tehran University of Medical Sciences, Tehran, Iran
Department of Human Anatomy and Cell Sciences, University of Manitoba, Manitoba, Canada
Biology of Breathing, Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada
Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Research Institute in Oncology and Hematology, Cancer Care Manitoba, University of Manitoba, Winnipeg, Canada
School of Animal and Veterinary Sciences, The University of Adelaide, Adelaide, Australia
Genomics Research Platform, School of Life Sciences, College of Science, Health and Engineering, La Trobe University, Melbourne, Australia
*Corresponding Addresses: Department of Human Anatomy and Cell Sciences University of Manitoba Manitoba Canada School of Animal and Veterinary Sciences The University of Adelaide Adelaide Australia Department of Stem Cells and Developmental Biology Cell Science Research Center Royan Institute for Stem Cell Biology and Technology ACECR Tehran Iran Emails:saeid.ghavami@umanitoba.ca,esmaeil.ebrahimie@adelaide.edu.au,mebrahimi@royaninstitute.org
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Sahranavardfard Parisa, Madjd Zahra, Emami Razavi Amirnader , Ghanadan Alireza, Firouzi Javad, Khosravani Pardis, Ghavami Saeid, Ebrahimie Esmaeil, Ebrahimi Marzieh. An Integrative Analysis of The Micro-RNAs Contributing in Stemness, Metastasis and B-Raf Pathways in Malignant Melanoma and Melanoma Stem Cell. Cell J. 2021; 23(3): 261-272.

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.