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miR-141-3p 通过成纤维细胞生长因子 13 介导的丝裂原活化蛋白激酶轴抑制人皮肤黑色素瘤生长和转移的作用。

The inhibitory role of microRNA-141-3p in human cutaneous melanoma growth and metastasis through the fibroblast growth factor 13-mediated mitogen-activated protein kinase axis.

机构信息

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.

出版信息

Melanoma Res. 2023 Dec 1;33(6):492-505. doi: 10.1097/CMR.0000000000000873. Epub 2023 Mar 21.

Abstract

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.

摘要

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。

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