当前位置: X-MOL 学术Mol. Ther. Oncol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
miR-140-3p Inhibits Cutaneous Melanoma Progression by Disrupting AKT/p70S6K and JNK Pathways through ABHD2.
Molecular Therapy: Oncology ( IF 5.3 ) Pub Date : 2020-03-30 , DOI: 10.1016/j.omto.2020.03.009
Yuanmin He 1 , Yan Yang 2 , Yongmei Liao 1 , Jixiang Xu 1 , Li Liu 1 , Changqiang Li 1 , Xia Xiong 1
Affiliation  

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 abhydrolase domain containing 2 (ABHD2) 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, in vivo 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.



中文翻译:

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

由于皮肤黑色素瘤 (CM) 是最致命的人类肿瘤之一,因此重大治疗进展至关重要。miR-140-3p 已被认为可作为一系列恶性肿瘤的抑制因子,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 生存率较差密切相关。此外,miR-140-3p的过表达显着抑制不同细胞系来源的CM细胞的细胞增殖、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测定,我们揭示了含有 2 ( ABHD2 )的脱氢酶结构域是 CM 细胞中 miR-140-3p 的靶标。ABHD2 的上调可逆转 CM 细胞中 miR-140-3p 的肿瘤抑制作用。此外,miR-140-3p靶向的ABHD2在CM细胞中JNK信号传导的激活和AKT/p70S6K通路的抑制中发挥作用。最后,体内结果强烈表明 miR-140-3p 对 CM 生长和转移具有抑制作用。总的来说,我们的研究结果强调了 miR-140-3p 通过 ABHD2 在 CM 中具有新的抗肿瘤功能。

更新日期:2020-03-30
down
wechat
bug