本文關(guān)鍵詞：PARD6A在卵巢癌中的作用機(jī)制研究　出處：《江蘇大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： PARD6A 卵巢癌 極性 遷移侵潤

【摘要】：分割缺陷蛋白6同源物α(Partitioning defective 6 homolog alpha,PARD6A)基因目前的研究主要聚焦在它作為細(xì)胞極化和細(xì)胞不對稱分裂的一個(gè)重要的分子支架蛋白的作用,盡管日前已有少量文獻(xiàn)報(bào)道了該基因可能與乳腺癌及肺癌的發(fā)生發(fā)展有關(guān)[1,2]。并且多篇文獻(xiàn)報(bào)道,極性蛋白很有可能影響腫瘤的遷移和侵潤。這個(gè)基因在卵巢癌中還未曾研究過,對這個(gè)基因在卵巢癌的作用和機(jī)制的研究,有可能定義出全新的卵巢癌靶向基因,用以啟動(dòng)新的靶向藥物研究。因此,以PARD6A基因?yàn)槟繕?biāo),實(shí)驗(yàn)首先考察PARD6A基因與卵巢癌的相關(guān)性。通過特異性沉默或過表達(dá)PARD6A基因,檢測了該基因?qū)β殉舶┘?xì)胞株功能的影響,此外,進(jìn)一步研究了PARD6A基因的蛋白表達(dá)量與臨床卵巢癌腫瘤相關(guān)性,在探索了臨床相關(guān)的基礎(chǔ)上,進(jìn)一步研究了PARD6A在卵巢癌中的作用機(jī)制。經(jīng)免疫印跡技術(shù)檢測到,PARD6A基因在漿液性卵巢癌細(xì)胞株SKOV3和A2780是異常高表達(dá)的;經(jīng)免疫組織化學(xué)技術(shù)檢測到PARD6A基因的蛋白在漿液性和粘液性卵巢腫瘤臨床組織樣本中高表達(dá)(其中漿液性是卵巢癌中最常見的組織學(xué)類型),比在正常卵巢組織中的表達(dá)顯著高。經(jīng)細(xì)胞劃痕實(shí)驗(yàn)、Transwell小室法、吸附實(shí)驗(yàn)及免疫熒光技術(shù)等檢測到,沉默PARD6A基因,抑制了卵巢癌細(xì)胞株遷移、侵潤能力和減弱吸附能力等;同時(shí),PARD6A過量表達(dá)促進(jìn)了錨定非依賴性生長、細(xì)胞的遷移和侵潤等。經(jīng)卵巢癌的小鼠肺轉(zhuǎn)移模型實(shí)驗(yàn),驗(yàn)證出以小發(fā)卡RNA(short hairpin RNA,shRNA)沉默PARD6A基因,可以在小鼠體內(nèi)能夠抑制卵巢癌細(xì)胞SKOV3的轉(zhuǎn)移;對于PARD6A對卵巢癌抑制遷移和侵潤的機(jī)制,本課題初步檢測到PARD6A基因可能影響了Cdc42和RhoA介導(dǎo)的細(xì)胞遷移和侵潤相關(guān)的信號通路。綜上所述,本課題旨在考察PARD6A基因在卵巢癌的作用和機(jī)制,希望因此能發(fā)現(xiàn)全新的卵巢癌靶向基因,用以改善卵巢癌的治療和預(yù)后,防止腫瘤的惡化和復(fù)發(fā)。
[Abstract]:The fragment defect protein 6 congener 偽 -partitioning defective 6 homolog alpha. The current study of the PARD6A) gene focuses on its role as an important molecular scaffold protein for cell polarization and asymmetric cell division. Although a small amount of literature has reported that the gene may be related to the occurrence and development of breast cancer and lung cancer. [The polarity protein may affect tumor migration and invasion. This gene has not been studied in ovarian cancer, and the role and mechanism of this gene in ovarian cancer have been studied. It may be possible to define new ovarian cancer targeting genes to initiate new targeted drug research. Therefore, target the PARD6A gene. Firstly, the relationship between PARD6A gene and ovarian cancer was investigated. The effect of PARD6A gene on ovarian cancer cell line function was detected by specific silencing or overexpression of PARD6A gene. The relationship between the protein expression of PARD6A gene and clinical ovarian cancer was further studied. The mechanism of PARD6A in ovarian cancer was further studied and detected by Western blotting. The expression of PARD6A gene was abnormally high in serous ovarian cancer cell lines SKOV3 and A2780. The protein of PARD6A gene was detected by immunohistochemistry in the clinical samples of serous and mucinous ovarian tumors (serous is the most common histological type of ovarian cancer). The expression of PARD6A gene was significantly higher than that in normal ovarian tissue. The PARD6A gene was silenced by cell scratch assay, transwell chamber assay, adsorption assay and immunofluorescence technique. Inhibition of ovarian cancer cell line migration, invasion ability and reduced adsorption ability, etc. At the same time, the overexpression of PARD6A promoted anchoring independent growth, cell migration and invasion. The silencing of PARD6A gene with small hairpin RNA(short hairpin RNAs was verified. The SKOV3 metastasis of ovarian cancer cells could be inhibited in mice. The mechanism of inhibition of migration and invasion of ovarian cancer by PARD6A. In this study, we preliminarily detected that PARD6A gene may affect Cdc42 and RhoA mediated cell migration and invasion signal pathway. The purpose of this study is to investigate the role and mechanism of PARD6A gene in ovarian cancer, so as to find a novel target gene for ovarian cancer in order to improve the treatment and prognosis of ovarian cancer and prevent the deterioration and recurrence of ovarian cancer.
【學(xué)位授予單位】：江蘇大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.31

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 吳為;李琴山;宋偉;繆時(shí)英;王琳芳;;串聯(lián)親和純化技術(shù)篩選Bat3的相互作用蛋白質(zhì)[J];中國醫(yī)學(xué)科學(xué)院學(xué)報(bào);2014年01期

，

本文編號：1439943