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微小RNA-524-5p在人垂体瘤衍生细胞系中发挥肿瘤抑制作用。

MicroRNA-524-5p Functions as a Tumor Suppressor in a Human Pituitary Tumor-Derived Cell Line.

作者信息

Zhen Wang, Qiu Du, Zhiyong Chen, Xin Wang, Mengyao Jian, Dimin Zhu, Chonghui Hu, Haijun Wang, Yonghong Zhu

机构信息

Department of Histology and Embryology, Medical school of Sun Yat-sen University, Guangzhou, Guangdong, China.

Key Laboratory of Functional Molecules from Marine Microorganisms, Department of Education of Guangdong Province, Sun Yat-sen University, Guangzhou, Guangdong, China.

出版信息

Horm Metab Res. 2017 Jul;49(7):550-557. doi: 10.1055/s-0043-106437. Epub 2017 May 4.

Abstract

Clinical nonfunctional pituitary adenomas (NFAs) account for about 40% of pituitary adenomas with almost no clinically relevant hormonal symptoms. Increasing evidence shows that many microRNAs are involved in the development and progression of pituitary adenomas. MicroRNA-524-5p (miR-524-5p) has been reported to cause characteristic alterations in various tumors. However, the functional importance of miR-524-5p in NFAs remains unknown. The aim of this study was to explore the effects of overexpressing miR-524-5p on the proliferation, migration, invasion, and tumorigenicity of pituitary-derived folliculostellate (PDFS) cells using lentiviral transfection. Interestingly, the results showed that overexpressing miR-524-5p downregulated pituitary tumor-transforming gene 1 (PTTG1) binding factor (PBF) expression at both mRNA and protein levels and significantly attenuated cell proliferation, clonogenicity, migration, and invasion in vitro. Moreover, enhancing miR-524-5p blocked tumor growth in a nude mouse xenograft model in vivo. These findings suggest that miR-524-5p appears to play a critical role in the regulation of biological properties of PDFS cells, and may represent a potential therapeutic target for NFAs.

摘要

临床无功能垂体腺瘤(NFAs)约占垂体腺瘤的40%,几乎没有临床相关的激素症状。越来越多的证据表明,许多微小RNA参与垂体腺瘤的发生和发展。据报道,微小RNA-524-5p(miR-524-5p)会在各种肿瘤中引起特征性改变。然而,miR-524-5p在NFAs中的功能重要性仍不清楚。本研究的目的是利用慢病毒转染探讨过表达miR-524-5p对垂体来源的滤泡星状细胞(PDFS)增殖、迁移、侵袭和致瘤性的影响。有趣的是,结果显示过表达miR-524-5p在mRNA和蛋白质水平上均下调垂体肿瘤转化基因1(PTTG1)结合因子(PBF)的表达,并显著减弱体外细胞增殖、克隆形成、迁移和侵袭。此外,增强miR-524-5p可在体内裸鼠异种移植模型中抑制肿瘤生长。这些发现表明,miR-524-5p似乎在PDFS细胞生物学特性的调节中起关键作用,可能是NFAs的一个潜在治疗靶点。

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