Sahranavardfard Parisa, Madjd Zahra, Emami Razavi Amir Nader, Ghanadan Ali Reza, Firouzi Javad, Khosravani Pardis, Ghavami Saeid, Ebrahimie Esmaeil, Ebrahimi Marzieh
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.
Cell J. 2021 Aug;23(3):261-272. doi: 10.22074/cellj.2021.7311. Epub 2021 Jul 17.
Epithelial-mesenchymal transition (EMT) and the stemness potency in association with 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.
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.
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 and expression.
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.
上皮-间质转化（EMT）以及与突变相关的干性潜能对于黑色素瘤的进展至关重要。最近，微小RNA（miRNA）已被引入作为大多数肿瘤中多种致癌功能的调节因子。因此，识别和解释这些miRNA的表达模式至关重要。本研究旨在寻找调节黑色素瘤发展中所有三个重要途径的常见miRNA。
在本实验研究中，根据当前文献以及与现有数据库的交叉分析，选择了18种对EMT有重要贡献且在调节自我更新和BRAF途径中起作用的miRNA。随后，在20例黑色素瘤患者、正常组织、患者血清和对照受试者以及黑色素球中评估了它们的表达模式。使用模式发现和综合调控网络分析来寻找黑色素瘤进展中最重要的miRNA。
在18种选定的miRNA中，miR-205、-141、-203、-15b和-9在肿瘤样本中的表达与正常组织相比存在差异。其中，miR-205、-15b和-9在血清样本和健康供体中显著表达。属性加权和决策树（DT）分析表明，miR-205、-203、-9和-15b的组合可通过影响 和 表达来调节自我更新和EMT过程。
我们在此提出，miR-205、-15b、-203、-9模式是与黑色素瘤状态、恶性细胞的多能性、增殖和运动性相关的关键miRNA。然而，需要进一步研究以发现上述miRNA组合效应的潜在机制。
