BRD4通过SHH信号通路诱导甲状腺癌细胞增殖、侵袭与迁移

发布时间：2018-07-03 19:06

本文选题：甲状腺癌 + 溴样结构域蛋白　；参考：《中国癌症杂志》2017年11期

【摘要】：背景与目的:甲状腺癌是目前发病率最高的内分泌系统恶性肿瘤之一,目前的综合治疗手段虽然效果较好,但是部分患者在随后的治疗中会出现继发性摄碘率下降,131I治疗效果差,从而导致复发及远处转移。近年来的研究发现,溴样结构域蛋白4(double bromodomain-containing protein 4,BRD4)可促进多种恶性肿瘤的进展,因此本研究旨在探究BRD4在甲状腺乳头状癌(papillary thyroid cancer,PTC)细胞中的作用,寻找治疗甲状腺癌的特异性靶点。方法:应用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)检测PTC组织和癌周组织中BRD4的表达差异,应用si BRD4干扰基因转染PTC细胞株TPC-1,应用蛋白[质]印迹法(Western blot)检验沉默效果,通过MTT实验、平板克隆实验、Transwell小室侵袭与迁移实验检验沉默BRD4前后PTC细胞株TPC-1活力、增殖、迁移及侵袭等生物学行为的变化。进一步应用Western blot及RTFQ-PCR检测钠碘转运体(sodium iodide symporter,NIS)基因及蛋白的表达变化,以及SHH信号通路下游基因SHH、GLI1表达变化情况。结果:BRD4在PTC组织中表达明显增高(P0.05);在体外实验中BRD4沉默后PTC细胞株TPC-1的细胞活力、增殖、迁移与侵袭能力下降。此外,BRD4沉默后NIS基因及蛋白表达增高,SHH信号通路下游基因SHH、GLI1表达降低(P0.05)。结论:BRD4通过上调SHH信号通路相关基因促进PTC细胞的侵袭与迁移,沉默BRD4可以促进NIS的表达,BRD4有望成为治疗甲状腺癌的新靶点。
[Abstract]:Background & objective: thyroid carcinoma is one of the most common endocrine malignant tumors. However, in some patients, the secondary iodine uptake rate decreased with 131I, which resulted in recurrence and distant metastasis. In recent years, it has been found that brominoid domain protein 4 (double bromodomain-containing protein 4n BRD4) can promote the development of many kinds of malignant tumors. Therefore, the purpose of this study is to explore the role of BRD4 in (papillary thyroid cancer-PTC cells of papillary thyroid carcinoma and to find specific targets for the treatment of thyroid carcinoma. Methods: the expression of BRD4 was detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). Si BRD4 interference gene was used to transfect the PTC cell line TPC-1, and the silencing effect was detected by Western blot. MTT assay, transwell chamber invasion and migration assay were used to detect the changes of TPC-1 activity, proliferation, migration and invasion of PTC cell line before and after BRD4 silencing. Western blot and RTFQ-PCR were used to detect the expression of (sodium iodide symporter NIS) gene and protein, and the downstream gene SHHHnGLI1 expression in SHH signaling pathway. Results the expression of 1% BRD4 was significantly increased in PTC tissue (P0.05), and the cell viability, proliferation, migration and invasion of PTC cell line TPC-1 were decreased after BRD4 silencing in vitro. In addition, the expression of NIS gene and protein increased after the silencing of BRD4, and the expression of the downstream gene SHHnGLI1 in the SHH signaling pathway decreased (P0.05). Conclusion by up-regulation of SHH signaling pathway genes, the invasion and migration of PTC cells can be promoted by 1: BRD4. Silencing BRD4 can promote the expression of NIS. BRD4 may be a new target for the treatment of thyroid carcinoma.
【作者单位】：潍坊医学院临床学院;潍坊市中医院乳腺甲状腺外科;
【基金】：潍坊市卫生局科研立项项目(2015WS006)
【分类号】：R736.1

【相似文献】