An Integrative Analysis of The Micro-RNAs Contributing in Stemness, Metastasis and B-Raf Pathways in Malignant Melanoma and Melanoma Stem Cell
Authors: Parisa Sahranavardfard, Zahra Madjd, Amirnader Emami Razavi, Alireza Ghanadan, Javad Firouzi, Pardis Khosravani, Saeid Ghavami, Esmaeil Ebrahimie, Marzieh Ebrahimi
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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 expressionpatterns 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.