Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine.
Shanghai Jiao Tong University School of Medicine.
Melanoma Res. 2023 Dec 1;33(6):492-505. doi: 10.1097/CMR.0000000000000873. Epub 2023 Mar 21.
Human cutaneous melanoma (CM) is a highly invasive malignancy arising from melanocytes, and accompanied by ever-increasing incidence and mortality rates worldwide. Interestingly, microRNAs (miRNAs) possess the ability to regulate CM cell biological functions, resulting in the aggressive progression of CM. Nevertheless, a comprehensive understanding of the underlying mechanism remains elusive. Accordingly, the current study sought to elicit the functional role of miR-141-3p in human CM cells in association with fibroblast growth factor 13 (FGF13) and the MAPK pathway. First, miR-141-3p expression patterns were detected in human CM tissues and cell lines, in addition to the validation of the targeting relationship between miR-141-3p and FGF13. Subsequently, loss- and gain-of-function studies of miR-141-3p were performed to elucidate the functional role of miR-141-3p in the malignant features of CM cells. Intriguingly, our findings revealed that FGF13 was highly expressed, whereas miR-141-3p was poorly expressed in the CM tissues and cells. Further analysis highlighted FGF13 as a target gene of miR-141-3p. Meanwhile, overexpression of miR-141-3p inhibited the proliferative, invasive, and migratory abilities of CM cells, while enhancing their apoptosis accompanied by downregulation of FGF13 and the MAPK pathway-related genes. Collectively, our findings highlighted the inhibitory effects of miR-141-3p on CM cell malignant properties via disruption of the FGF13-dependent MAPK pathway, suggesting a potential target for treating human CM.
人类皮肤黑色素瘤(CM)是一种源自黑色素细胞的高度侵袭性恶性肿瘤,其发病率和死亡率在全球范围内呈不断上升趋势。有趣的是,微小 RNA(miRNA)具有调节 CM 细胞生物学功能的能力,导致 CM 的侵袭性进展。然而,其潜在机制仍未被完全理解。因此,本研究旨在探讨 miR-141-3p 在人类 CM 细胞中与成纤维细胞生长因子 13(FGF13)和 MAPK 通路相关的功能作用。首先,检测了人类 CM 组织和细胞系中 miR-141-3p 的表达模式,并验证了 miR-141-3p 与 FGF13 之间的靶向关系。随后,进行了 miR-141-3p 的缺失和功能获得研究,以阐明 miR-141-3p 在 CM 细胞恶性特征中的功能作用。有趣的是,我们的研究结果表明,FGF13 在 CM 组织和细胞中高表达,而 miR-141-3p 表达水平较低。进一步的分析强调了 FGF13 是 miR-141-3p 的靶基因。同时,miR-141-3p 的过表达抑制了 CM 细胞的增殖、侵袭和迁移能力,同时促进了细胞凋亡,伴随着 FGF13 和 MAPK 通路相关基因的下调。综上所述,miR-141-3p 通过破坏 FGF13 依赖的 MAPK 通路抑制 CM 细胞恶性特性,为治疗人类 CM 提供了潜在的治疗靶点。