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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

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journal contribution
posted on 08.10.2021, 03:54 by P Sahranavardfard, Z Madjd, AE Razavi, A Ghanadan, J Firouzi, P Khosravani, S Ghavami, Esmaeil EbrahimieEsmaeil Ebrahimie, M Ebrahimi
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.

Funding

This study received grants from the Royan Institute (ID No: 91000426) and an external fund from Iran National Science Foundation (Grant #90003728). We also thank Elham Kalantari, Dedmer Schaafsma, Yashar Abbasnejad, Bahareh Fasihpour, Foroogh Sayyahpour, Azam Samadian, Fatemeh Ganji, Sara Pahlevan, and Ali Jahanbin for their technical assistance. The authors declare no conflicts of interest.

History

Publication Date

01/08/2021

Journal

Cell Journal

Volume

23

Issue

3

Pagination

12p. (p. 261-272)

Publisher

Royan Institute

ISSN

2228-5806

Rights Statement

The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.

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