Zhen Wang, Qiu Du, Zhiyong Chen, Xin Wang, Mengyao Jian, Dimin Zhu, Chonghui Hu, Haijun Wang, Yonghong Zhu
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.
Horm Metab Res. 2017 Jul;49(7):550-557. doi: 10.1055/s-0043-106437. Epub 2017 May 4.
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.
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。