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微小RNA-522通过靶向蛋白磷酸酶1A刺激转化生长因子-β/信号转导和转录激活因子信号通路并促进骨肉瘤肿瘤发生。

miR-522 stimulates TGF-β/Smad signaling pathway and promotes osteosarcoma tumorigenesis by targeting PPM1A.

作者信息

Xu Xiqiang, Liu Mengmeng

机构信息

Department of Spine Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China.

Department of Anesthesiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China.

出版信息

J Cell Biochem. 2019 Oct;120(10):18425-18434. doi: 10.1002/jcb.29160. Epub 2019 Jun 12.

Abstract

Osteosarcoma (OS) is identified as an aggressive malignancy of the skeletal system and normally occurs among young people. It is well accepted that microRNAs are implicated in biological activities of diverse tumors. Although miR-522 has been proved to elicit oncogenic properties in a wide range of human cancers, the physiological function and latent mechanism of miR-522 in OS tumorigenesis remain largely to be probed. In the current study, we certified that miR-522 was highly expressed in OS cells and presented carcinogenic function by contributing to cell proliferation, migration, and EMT progression whereas dampening cell apoptosis. In addition, miR-522 provoked TGF-β/Smad pathway through targeting PPM1A. Finally, the results of mechanism experiments elucidated that miR-522 stimulated TGF-β/Smad pathway to induce the development of OS via targeting PPM1A, which exposed that miR-522 may become a promising curative target for OS patients.

摘要

骨肉瘤(OS)是一种侵袭性的骨骼系统恶性肿瘤,通常发生在年轻人中。众所周知,微小RNA参与多种肿瘤的生物学活动。尽管已证明miR-522在多种人类癌症中具有致癌特性,但miR-522在骨肉瘤发生中的生理功能和潜在机制仍有待深入探究。在本研究中,我们证实miR-522在骨肉瘤细胞中高表达,并通过促进细胞增殖、迁移和上皮-间质转化进程,同时抑制细胞凋亡,发挥致癌作用。此外,miR-522通过靶向PPM1A激活TGF-β/Smad信号通路。最后,机制实验结果表明,miR-522通过靶向PPM1A激活TGF-β/Smad信号通路,从而诱导骨肉瘤的发生发展,这表明miR-522有望成为骨肉瘤患者的治疗靶点。

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