本文選題：甲狀腺癌 + 溴樣結(jié)構(gòu)域蛋白　； 參考：《中國癌癥雜志》2017年11期

【摘要】：背景與目的:甲狀腺癌是目前發(fā)病率最高的內(nèi)分泌系統(tǒng)惡性腫瘤之一,目前的綜合治療手段雖然效果較好,但是部分患者在隨后的治療中會出現(xiàn)繼發(fā)性攝碘率下降,131I治療效果差,從而導(dǎo)致復(fù)發(fā)及遠處轉(zhuǎn)移。近年來的研究發(fā)現(xiàn),溴樣結(jié)構(gòu)域蛋白4(double bromodomain-containing protein 4,BRD4)可促進多種惡性腫瘤的進展,因此本研究旨在探究BRD4在甲狀腺乳頭狀癌(papillary thyroid cancer,PTC)細胞中的作用,尋找治療甲狀腺癌的特異性靶點。方法:應(yīng)用實時熒光定量聚合酶鏈反應(yīng)(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)檢測PTC組織和癌周組織中BRD4的表達差異,應(yīng)用si BRD4干擾基因轉(zhuǎn)染PTC細胞株TPC-1,應(yīng)用蛋白[質(zhì)]印跡法(Western blot)檢驗沉默效果,通過MTT實驗、平板克隆實驗、Transwell小室侵襲與遷移實驗檢驗沉默BRD4前后PTC細胞株TPC-1活力、增殖、遷移及侵襲等生物學(xué)行為的變化。進一步應(yīng)用Western blot及RTFQ-PCR檢測鈉碘轉(zhuǎn)運體(sodium iodide symporter,NIS)基因及蛋白的表達變化,以及SHH信號通路下游基因SHH、GLI1表達變化情況。結(jié)果:BRD4在PTC組織中表達明顯增高(P0.05);在體外實驗中BRD4沉默后PTC細胞株TPC-1的細胞活力、增殖、遷移與侵襲能力下降。此外,BRD4沉默后NIS基因及蛋白表達增高,SHH信號通路下游基因SHH、GLI1表達降低(P0.05)。結(jié)論:BRD4通過上調(diào)SHH信號通路相關(guān)基因促進PTC細胞的侵襲與遷移,沉默BRD4可以促進NIS的表達,BRD4有望成為治療甲狀腺癌的新靶點。
[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.
【作者單位】： 濰坊醫(yī)學(xué)院臨床學(xué)院;濰坊市中醫(yī)院乳腺甲狀腺外科;
【基金】：濰坊市衛(wèi)生局科研立項項目(2015WS006)
【分類號】：R736.1

【相似文獻】

相關(guān)期刊論文 前3條

1 胡艷紅;黎七雄;;原發(fā)性肝癌中SHH信號通路的研究[J];科技信息;2012年30期

2 陳霖;楊勇;徐偉;楊宏新;成綏生;高維實;;BARD1和Aurora-A在甲狀腺癌中的表達及意義[J];內(nèi)蒙古醫(yī)學(xué)雜志;2014年05期

3 薛江;張瑞明;;甲狀腺癌術(shù)前診斷的研究進展[J];內(nèi)蒙古醫(yī)學(xué)雜志;2014年05期

相關(guān)博士學(xué)位論文 前3條

1 趙健潔;長鏈非編碼RNA-ANRIL通過TGF beta/Smad信號通路調(diào)控甲狀腺癌細胞侵襲和轉(zhuǎn)移研究[D];第三軍醫(yī)大學(xué);2017年

2 高雪梅;BRD4相關(guān)的甲狀腺癌分子機制研究及微小乳頭狀甲狀腺癌患者臨床轉(zhuǎn)歸分析[D];華中科技大學(xué);2016年

3 劉靳波;SHH信號通路核轉(zhuǎn)錄因子Gli1在肝癌中的作用研究[D];重慶醫(yī)科大學(xué);2009年

相關(guān)碩士學(xué)位論文 前1條

1 吳丹;乙�；揎楅喿x器BRD4作為食管鱗癌治療靶點的研究[D];浙江大學(xué);2016年

，

本文編號：2094700