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miR-140-3p通过ABHD2破坏AKT/p70S6K和JNK信号通路来抑制皮肤黑色素瘤进展。

miR-140-3p Inhibits Cutaneous Melanoma Progression by Disrupting AKT/p70S6K and JNK Pathways through ABHD2.

作者信息

He Yuanmin, Yang Yan, Liao Yongmei, Xu Jixiang, Liu Li, Li Changqiang, Xiong Xia

机构信息

Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.

Department of Public Health, Southwest Medical University, Luzhou, Sichuan 646000, China.

出版信息

Mol Ther Oncolytics. 2020 Mar 30;17:83-93. doi: 10.1016/j.omto.2020.03.009. eCollection 2020 Jun 26.

Abstract

Because cutaneous melanoma (CM) is one of the most lethal human tumors, major treatment advances are vital. miR-140-3p has been suggested to act as a suppressor in a range of malignant tumors, implying its possible use as a biomarker for effective antineoplastic treatment. However, the potential role of miR-140-3p in CM and the underlying mechanism remain unclear. In the present study, we identified lower levels of miR-140-3p in both CM tissues and cell lines; this downregulation was strongly associated with worse CM survival. Additionally, overexpression of miR-140-3p significantly inhibited cell proliferation, migration, and invasion in CM cells with different cell line origins. Importantly, by means of both bioinformatics analysis and luciferase reporter assay, we revealed () to be a target of miR-140-3p in CM cells. Upregulation of ABHD2 reversed the tumor-suppressive effects of miR-140-3p in CM cells. Furthermore, miR-140-3p-targeted ABHD2 played a role in both activation of JNK signaling and inhibition of the AKT/p70S6K pathway in CM cells. Finally, results strongly suggested the suppressive effects of miR-140-3p on CM growth and metastasis. Collectively, our findings highlight a novel antineoplastic function for miR-140-3p in CM through ABHD2.

摘要

由于皮肤黑色素瘤(CM)是最致命的人类肿瘤之一,重大的治疗进展至关重要。miR-140-3p已被认为在一系列恶性肿瘤中起抑制作用,这意味着它有可能用作有效抗肿瘤治疗的生物标志物。然而,miR-140-3p在CM中的潜在作用及其潜在机制仍不清楚。在本研究中,我们发现CM组织和细胞系中miR-140-3p水平较低;这种下调与CM患者较差的生存率密切相关。此外,miR-140-3p的过表达显著抑制了不同细胞系来源的CM细胞的增殖、迁移和侵袭。重要的是,通过生物信息学分析和荧光素酶报告基因检测,我们发现()是CM细胞中miR-140-3p的一个靶标。ABHD2的上调逆转了miR-140-3p对CM细胞的肿瘤抑制作用。此外,miR-140-3p靶向的ABHD2在CM细胞中JNK信号通路的激活和AKT/p70S6K通路的抑制中均发挥作用。最后,结果强烈表明miR-140-3p对CM生长和转移具有抑制作用。总体而言,我们的研究结果突出了miR-140-3p通过ABHD2在CM中发挥的新型抗肿瘤功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e378/7163049/672deed9a92e/fx1.jpg

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