微小RNA-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在人类皮肤黑色素瘤生长和转移中的抑制作用。

IF 1.5 4区 医学 Q3 DERMATOLOGY Melanoma Research Pub Date : 2023-12-01 Epub Date: 2023-03-21 DOI:10.1097/CMR.0000000000000873
Haojan Yang, Jiateng Zhou, Dongdong Li, Shengbo Zhou, Xinyi Dai, Xinchao Du, Hailei Mao, Bin Wang
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引用次数: 0

摘要

人类皮肤黑色素瘤(CM)是一种由黑色素细胞引起的高度侵袭性恶性肿瘤,其发病率和死亡率在全球范围内不断上升。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,对其潜在机制的全面理解仍然难以捉摸。因此,目前的研究试图引发miR-141-3p在人类CM细胞中与成纤维细胞生长因子13(FGF13)和MAPK途径相关的功能作用。首先,除了验证miR-141-3p和FGF13之间的靶向关系外,还在人类CM组织和细胞系中检测到miR-141-3p的表达模式。随后,对miR-141-3p进行了功能丧失和获得研究,以阐明miR-141-3p在CM细胞恶性特征中的功能作用。有趣的是,我们的研究结果显示,FGF13在CM组织和细胞中高表达,而miR-141-3p在CM组织或细胞中低表达。进一步的分析强调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,同时增强了其凋亡,同时下调了FGF13和MAPK通路相关基因。总之,我们的研究结果强调了miR-141-3p通过破坏FGF13依赖性MAPK途径对CM细胞恶性特性的抑制作用,这表明它是治疗人类CM的潜在靶点。
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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.

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.

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来源期刊
Melanoma Research
Melanoma Research 医学-皮肤病学
CiteScore
3.40
自引率
4.50%
发文量
139
审稿时长
6-12 weeks
期刊介绍: ​​​​​​Melanoma Research is a well established international forum for the dissemination of new findings relating to melanoma. The aim of the Journal is to promote the level of informational exchange between those engaged in the field. Melanoma Research aims to encourage an informed and balanced view of experimental and clinical research and extend and stimulate communication and exchange of knowledge between investigators with differing areas of expertise. This will foster the development of translational research. The reporting of new clinical results and the effect and toxicity of new therapeutic agents and immunotherapy will be given emphasis by rapid publication of Short Communications. ​Thus, Melanoma Research seeks to present a coherent and up-to-date account of all aspects of investigations pertinent to melanoma. Consequently the scope of the Journal is broad, embracing the entire range of studies from fundamental and applied research in such subject areas as genetics, molecular biology, biochemistry, cell biology, photobiology, pathology, immunology, and advances in clinical oncology influencing the prevention, diagnosis and treatment of melanoma.
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