本文選題：TRIM24 + 膠質(zhì)細胞瘤�。� 參考：《第四軍醫(yī)大學》2014年博士論文

【摘要】：膠質(zhì)細胞瘤包括星形膠質(zhì)細胞瘤、少突膠質(zhì)細胞瘤、室管膜瘤以及混合型膠質(zhì)細胞瘤等。中樞神經(jīng)系統(tǒng)最常見的原發(fā)惡性腫瘤是惡性膠質(zhì)細胞瘤，涵蓋間變型星形細胞瘤(WHO Ⅲ級)、間變型少突膠質(zhì)細胞瘤(WHO Ⅲ級)和多形性膠質(zhì)母細胞瘤(也稱膠質(zhì)母細胞瘤，WHO Ⅳ級)。大多數(shù)惡性膠質(zhì)細胞瘤是膠質(zhì)母細胞瘤。盡管近年來手術技術、放療策略和化療方案取得了重大進展，間變型星形細胞瘤患者的中位總存活期為2-3年，間變型少突膠質(zhì)細胞瘤患者中位總存活期為3-5年，而膠質(zhì)母細胞瘤患者中位總存活期僅為12-15個月。因此，惡性膠質(zhì)細胞瘤成為腫瘤研究領域的迫切課題。腫瘤標志物的鑒定可以提高預后評估的準確度，增加常規(guī)治療的效率，并且開拓了分子靶向療法。 TRIM24(tripartite motif-containing24)也被稱為TIF1(transcription intermediaryfactor1)，是轉(zhuǎn)錄中介因子家族的創(chuàng)始成員。TRIM24蛋白的氨基末端有TRIM模體，即RING結(jié)構(gòu)域、B盒和回旋卷曲區(qū)，羧基末端有PHD和Bromo結(jié)構(gòu)域。其中，具有泛素-蛋白連接酶E3活性的RING結(jié)構(gòu)域能介導p53的泛素化降解，而PHD和Bromo結(jié)構(gòu)域識別特定修飾的組蛋白分子。此外，TRIM24蛋白中間段的LxxLL序列能夠配體依賴性地結(jié)合多種細胞核受體，而PxVxL序列可以結(jié)合HP1參與染色質(zhì)結(jié)構(gòu)改造。由于其蛋白結(jié)構(gòu)的多樣性，TRIM24與腫瘤的密切關系在近些年被逐漸揭示。對于肝癌，TRIM24是作為抑癌基因；但對于粒細胞白血病和乳腺癌，TRIM24則發(fā)揮癌基因功能。 比較基因組雜交實驗已發(fā)現(xiàn)大約1/3的膠質(zhì)母細胞瘤存在TRIM24基因片段的擴增，尤其是對于50歲以上的患者，提示TRIM24可能參與了膠質(zhì)細胞瘤的發(fā)生和發(fā)展。為了闡明它們之間可能存在的關系，我們收集手術標本檢測TRIM24表達水平，開展一系列體外和體內(nèi)實驗以研究其細胞分子機理，并探索相關的臨床意義。 1. TRIM24在膠質(zhì)細胞瘤中的過表達呈現(xiàn)病理級別依賴性的特征并且參與膠質(zhì)母細胞瘤的復發(fā) 免疫組化方法檢測TRIM24在15例正常腦組織、24例毛細胞型星形細胞瘤(WHOⅠ級)、57例彌漫型星形細胞瘤(WHOⅡ級)、63例間變型星形細胞瘤、297例初診膠質(zhì)母細胞瘤、48例復發(fā)性膠質(zhì)母細胞瘤以及44例少突膠質(zhì)細胞瘤中的表達情況。在正常腦膠質(zhì)組織和少突膠質(zhì)細胞瘤中，TRIM24免疫染色陰性或僅在少數(shù)細胞中顯示弱染色；但是在星形細胞瘤中，TRIM24呈現(xiàn)過表達，并且隨著病理級別的升高，其表達量也相應增加，只是在毛細胞型星形細胞瘤和彌漫型星形細胞瘤之間未見統(tǒng)計學差異。通過Westernblot檢測冷凍保存組織標本中的蛋白含量，進一步驗證了免疫組化所觀察到的TRIM24表達譜。將取自同一患者的初診和復發(fā)性膠質(zhì)母細胞瘤標本進行配對分析發(fā)現(xiàn)，TRIM24的表達在膠質(zhì)母細胞瘤復發(fā)時有所升高，尤其是對于初診時表達水平相對較低的病例。這些結(jié)果提示，TRIM24可能參與了膠質(zhì)細胞瘤的發(fā)生，并且其表達水平與膠質(zhì)細胞瘤的惡性程度之間存在著正相關關系。 2. TRIM24表達水平與初診膠質(zhì)母細胞瘤患者的預后具有負相關關系 隨訪工作從2009年開始，不斷納入病例并且更新資料，直至2013年結(jié)束，共記錄了297例初診膠質(zhì)母細胞瘤患者的年齡、性別、手術切除程度、KPS評分、化療狀態(tài)、總生存期(overall survival, OS)和無進展生存期(progression-free survival，PFS)等數(shù)據(jù)。采用Kaplan-Meier法繪制TRIM24低表達組和高表達組患者的生存曲線得出：低表達組的中位OS為13.9個月(95%CI，11.5-16.3個月)，而高表達組的中位OS為11.0個月(95%CI，10.6-11.4個月)；低表達組的中位PFS為6.5個月(95%CI，5.5-7.5個月)，而高表達組的中位PFS為5.3個月(95%CI，4.8-5.8個月)。log-rank檢驗發(fā)現(xiàn)低表達組和高表達組的OS和PFS之間均存在顯著性差異(P＜0.001)。多因素Cox比例風險回歸模型發(fā)現(xiàn)，KPS評分、年齡和TRIM24表達水平三者是影響OS的獨立預后因素，而KPS評分和TRIM24水平還是PFS的獨立預后影響因素。這些結(jié)果提示，檢測惡性標志物TRIM24的水平，并結(jié)合患者臨床指標綜合考慮，在一定程度上可以提高膠質(zhì)母細胞瘤患者預后評估的準確度；同時進一步說明了對于高度異質(zhì)性的單一病理級別的膠質(zhì)細胞瘤——膠質(zhì)母細胞瘤，TRIM24水平與腫瘤惡性程度之間仍然存在著正相關關系。 3. TRIM24在體外和體內(nèi)條件下促進膠質(zhì)細胞瘤生長 為了研究TRIM24促進膠質(zhì)細胞瘤惡性進展的機理，我們構(gòu)建了2種TRIM24干涉逆轉(zhuǎn)錄病毒、1種陰性對照逆轉(zhuǎn)錄病毒、過表達人TRIM24基因慢病毒以及陰性對照慢病毒，并將這些病毒感染人膠質(zhì)母細胞瘤細胞系，從而檢測TRIM24表達水平改變對膠質(zhì)細胞瘤生長的影響。細胞增殖曲線顯示，干涉TRIM24表達延長了T98和U87細胞的倍增時間。流式細胞儀測定細胞周期分布發(fā)現(xiàn)，TRIM24干涉的T98細胞的G2/M期比例減少，而過表達TRIM24的U251細胞的G2/M期比例增加。軟瓊脂克隆形成實驗得出，TRIM24干涉的T98和U87細胞形成的克隆不僅數(shù)量減少，，而且體積縮小。體內(nèi)實驗發(fā)現(xiàn)，穩(wěn)定干涉TRIM24表達的T98細胞喪失了裸鼠皮下成瘤能力，而陰性對照細胞仍然具有成瘤性。這些結(jié)果表明，TRIM24能夠促進膠質(zhì)細胞瘤的生長，所以針對TRIM24的靶向治療有望起到干擾膠質(zhì)細胞瘤進一步發(fā)展的作用。 4. TRIM24通過激活PI3K/Akt信號轉(zhuǎn)導促進膠質(zhì)細胞瘤生長 由于PI3K/Akt和Raf/MEK/ERK信號轉(zhuǎn)導途徑是與膠質(zhì)細胞瘤生長相關的主要通路，故采用Western blot檢測TRIM24干涉對Akt和ERK活化程度的影響，并進行TRIM24表達恢復實驗。干涉TRIM24表達引起p-Akt水平降低，同時p-ERK水平升高，反映了由于p-Akt減少后對Raf/MEK/ERK通路的抑制作用得到緩解。當TRIM24干涉的細胞感染過表達TRIM24的慢病毒時，TRIM24含量有一定程度的恢復，原先降低的p-Akt水平有所上升，而原先升高的p-ERK水平則有所回落。MTT實驗發(fā)現(xiàn)，與TRIM24低表達細胞相比，TRIM24高表達細胞的增殖對PI3K抑制劑LY294002和針對PIK3CA的siRNA更加敏感。Real-time RT-PCR和Western blot檢測發(fā)現(xiàn)，當干涉TRIM24表達時，PIK3CA表達水平下調(diào)。ChIP實驗顯示，TRIM24蛋白能夠結(jié)合T98和U87細胞中PIK3CA基因的啟動子。野生型TRIM24能夠在一定程度上恢復TRIM24干涉細胞的PIK3CA和p-Akt水平，而PHD-Bromo段缺失的TRIM24突變體則未見效果。這些結(jié)果說明，TRIM24對膠質(zhì)細胞瘤生長的促進作用是由PI3K/Akt信號通路所介導。 5. TRIM24促進膠質(zhì)細胞瘤的耐藥性 除了腫瘤生長，耐藥是惡性膠質(zhì)細胞瘤進展和復發(fā)的重要因素。為了研究TRIM24是否影響細胞對替莫唑胺的反應性，我們將TRIM24干涉和陰性對照細胞分別暴露于替莫唑胺作用之下。MTT實驗發(fā)現(xiàn)，干涉TRIM24表達可以增加替莫唑胺對T98和U87細胞的毒性。平板克隆形成實驗顯示，TRIM24干涉削弱了膠質(zhì)瘤細胞在替莫唑胺作用下形成克隆的能力。將TRIM24干涉的T98細胞暴露于替莫唑胺1周后，可見明顯的caspase-7剪切活化體、TUNEL標記信號以及Annexin V著色，而對照組細胞卻很少有凋亡發(fā)生。體內(nèi)實驗同樣發(fā)現(xiàn)TRIM24干涉能夠提高替莫唑胺的治療效果。而且，在臨床背景下，TRIM24低表達的膠質(zhì)母細胞瘤患者能夠從化療中獲益，而TRIM24高表達組患者的預后不會因為化療而有所改變。這些結(jié)果說明，TRIM24可以促進膠質(zhì)細胞瘤的耐藥性，將TRIM24干涉和化療聯(lián)合應用有望提高膠質(zhì)母細胞瘤的治療效果。 6. TRIM24通過PI3K/Akt/NF-κB信號轉(zhuǎn)導調(diào)節(jié)耐藥基因MGMT的表達 由于DNA修復酶MGMT在替莫唑胺耐藥中發(fā)揮著關鍵作用，所以我們檢測了TRIM24干涉對MGMT的mRNA和蛋白水平的影響。Western blot實驗發(fā)現(xiàn)，TRIM24干涉導致T98細胞的MGMT蛋白含量減少。Real-time RT-PCR實驗顯示，TRIM24干涉是在轉(zhuǎn)錄水平上調(diào)節(jié)MGMT的表達。雖然ChIP實驗未見TRIM24結(jié)合MGMT基因啟動子，但是雙熒光素酶報告基因檢測發(fā)現(xiàn)，TRIM24干涉引起NF-κB轉(zhuǎn)錄活性降低，即與抑制PI3K/Akt信號轉(zhuǎn)導的結(jié)果類似。TRIM24干涉對MGMT表達的影響可以被重新引入的TRIM24所逆轉(zhuǎn)，但是如果同時用siRNA干涉NF-κB亞單位p65的編碼基因RelA的表達，MGMT水平的恢復則受到阻斷。這些結(jié)果說明，TRIM24對MGMT表達的調(diào)控作用是(或者至少部分是)由PI3K/Akt/NF-κB途徑所介導的。
[Abstract]:Glioblastoma includes astrocytoma, oligodendroglioma, ependymoma, and mixed glioblastoma. The most common primary malignant tumor of the central nervous system is malignant glioblastoma, which covers the variant type astrocytoma (WHO grade III), oligodendroglioma (WHO grade III) and glioblastoma. (also known as glioblastoma, WHO IV). Most of the malignant glioblastomas are glioblastoma. Although significant progress has been made in surgical techniques, radiotherapy strategies and chemotherapy schemes in recent years, the median survival time of patients with mesenchymal astrocytoma is 2-3 years, and the median survival time of the patients with oligodendroglioma is 3-5 years, and the glue is in glue. The median survival period of the patients with blastoma is only 12-15 months. Therefore, malignant glioblastoma has become an urgent subject in the field of cancer research. Identification of tumor markers can improve the accuracy of prognosis assessment, increase the efficiency of conventional therapy, and develop molecular targeting therapy.
TRIM24 (tripartite motif-containing24), also known as TIF1 (transcription intermediaryfactor1), is the original member of the transcriptional mediator family, the amino terminal of the amino terminal of the.TRIM24 protein has TRIM modules, namely the RING domain, B box and cyclotron curling area, and the carboxyl terminal has PHD and Bromo domains. The domain can mediate the ubiquitination of p53, while the PHD and Bromo domains identify the specific modified histone molecules. In addition, the LxxLL sequence of the intermediate segment of the TRIM24 protein can be ligands dependent on a variety of nuclear receptors, and the PxVxL sequence can be combined with HP1 to modify the chromatin structure. Because of its protein structure diversity, TRIM24 and swelling The close relationship between tumors has been gradually revealed in recent years. For liver cancer, TRIM24 is a tumor suppressor gene, but for granulocytic leukemia and breast cancer, TRIM24 plays the oncogene function.
Comparative genomic hybridization has found that approximately 1/3 glioblastoma exists TRIM24 gene fragment amplification, especially for patients over 50 years old, suggesting that TRIM24 may be involved in the occurrence and development of glioblastoma. In order to clarify the possible relationship between them, we collect surgical specimens to detect the level of TRIM24 expression and develop A series of in vitro and in vivo experiments were carried out to study the cellular molecular mechanism and explore the clinical relevance.
1. the overexpression of TRIM24 in glioblastoma is pathological grade dependent and participates in the recurrence of glioblastoma.
Immunohistochemical method was used to detect TRIM24 in 15 normal brain tissues, 24 cases of hair cell type astrocytoma (WHO grade I), 57 cases of diffuse astrocytoma (WHO class II), 63 cases of Intervariant astrocytoma, 297 newly diagnosed glioblastoma, 48 recurrent glioblastoma, and 44 oligodendroglioma. In both qualitative and oligodendrogliomas, TRIM24 immunostaining is negative or only a few cells show weak staining. But in astrocytoma, TRIM24 is overexpressed, and its expression increases with the rise of pathological grade, only between the hair cell type astrocytoma and the diffuse astrocytoma. The protein content in the frozen tissue specimens was detected by Westernblot, and the TRIM24 expression profile observed by immunohistochemistry was further verified. The paired analysis of the primary and recurrent glioblastoma specimens from the same patient showed that the expression of TRIM24 increased in the recurrence of glioblastoma, especially in the case of recurrent glioblastoma. These results suggest that TRIM24 may be involved in the occurrence of glioma and that there is a positive correlation between the level of the expression and the malignancy of glioma.
2. the level of TRIM24 expression is negatively correlated with the prognosis of patients with newly diagnosed glioblastoma.
The follow-up work began in 2009 and continued to be included in cases and updated until the end of 2013. A total of 297 patients with newly diagnosed glioblastoma were recorded, including age, sex, surgical excision, KPS, chemotherapy, total survival (overall survival, OS), and progression free survival (progression-free survival, PFS). The an-Meier method was used to draw the survival curve of TRIM24 low expression group and high expression group. The median OS of the low expression group was 13.9 months (95%CI, 11.5-16.3 month), while the middle OS in the high expression group was 11 months (95%CI, 10.6-11.4 month), and the median PFS in the low expression group was 6.5 months (95%CI, 5.5-7.5 month), while the median PFS in the high expression group was 5.3. There was a significant difference between the OS and PFS in the low expression group and the high expression group (P < 0.001). The multiple factor Cox proportional risk regression model found that KPS score, age and TRIM24 expression level three were independent preconditioning factors affecting OS, while KPS score and TRIM24 level were the independent prognostic factors, and the independent prognosis was also found to be an independent prognosis. These results suggest that the detection of the level of the malignant marker TRIM24 and the combination of the patient's clinical indicators can improve the accuracy of the prognosis evaluation of the patients with glioblastoma to a certain extent, and further explain the single pathological grade of glioblastoma, glioblastoma, TRI, which is highly heterogeneous. There is still a positive correlation between the level of M24 and malignancy of tumor.
3. TRIM24 promotes glioma growth in vitro and in vivo.
In order to study the mechanism of TRIM24 to promote the malignant progression of glioblastoma, we constructed 2 kinds of TRIM24 interfering retroviruses, 1 negative control retroviruses, TRIM24 gene lentivirus and negative control lentivirus, and the virus infection of human glioblastoma cell lines, so as to detect the change of TRIM24 expression level to glue The cell proliferation curve showed that interferometric TRIM24 expression extended the doubling time of T98 and U87 cells. Flow cytometry detected cell cycle distribution, the G2/M phase ratio of TRIM24 interfered T98 cells decreased, while the G2/M phase of U251 cells over expressed TRIM24 increased. The soft agar clone formation experiment obtained, TRIM24, TRIM24. The clones formed by interfered T98 and U87 cells are not only reduced in quantity but also in size. In vivo experiments have found that T98 cells that stably interfere with TRIM24 expression have lost the ability to tumour subcutaneously in nude mice, while negative control cells still have tumorigenicity. These results suggest that TRIM24 can promote the growth of glioma, so the targeting of TRIM24 is targeted. Treatment is expected to play a role in further development of glioma.
4. TRIM24 promotes glioma growth by activating PI3K/Akt signal transduction.
As PI3K/Akt and Raf/MEK/ERK signal transduction pathways are the main pathways associated with the growth of glioblastoma, Western blot is used to detect the effect of TRIM24 interference on the activation of Akt and ERK and to restore the TRIM24 expression. The interference TRIM24 expression causes p-Akt level to decrease, and the p-ERK level increases at the same time, reflecting the decrease of p-Akt. The inhibition of the Raf/MEK/ERK pathway was alleviated. When the TRIM24 interfered cells infected the TRIM24's lentivirus, the TRIM24 content was restored to a certain extent, and the previously reduced p-Akt level had increased, while the previously elevated p-ERK level was reduced to the.MTT experiment, and the TRIM24 high expression cells were compared with the TRIM24 low expression cells. The proliferation of the PI3K inhibitor LY294002 and the siRNA for the PIK3CA were more sensitive to.Real-time RT-PCR and Western blot detection. When the interference TRIM24 expression, PIK3CA expression level down.ChIP experiment showed that the TRIM24 protein could combine the promoter and the promoter of the gene. The PIK3CA and p-Akt levels of the cells were interfered, while the TRIM24 mutant of the PHD-Bromo segment was not effective. These results suggest that the promotion of TRIM24 on the growth of glioma is mediated by the PI3K/Akt signaling pathway.
5. TRIM24 to promote the drug resistance of glioma
In addition to tumor growth, drug resistance is an important factor in the progression and recurrence of malignant glioblastoma. In order to study whether TRIM24 affects the reactivity of cells to temozolomide, we found that TRIM24 interference and negative control cells were exposed to the action of temozolomide, respectively, in.MTT experiment. The interference of TRIM24 expression could increase the effect of temozolomide on T98 and U87. TRIM24 interference weakened the ability of glioma cells to form clones under the action of temozolomide. The TRIM24 interfered T98 cells were exposed to temozolomide for 1 weeks, and obvious caspase-7 shear activator, TUNEL marker signal and Annexin V coloring were seen, while few cells in the control group were apoptotic. In vivo experiments also found that TRIM24 interference could improve the therapeutic effect of temozolomide. In the clinical context, patients with TRIM24 low expression of glioblastoma could benefit from chemotherapy, while the prognosis of the TRIM24 high expression group was not altered by chemotherapy. These results suggest that TRIM24 can promote glioblastoma. The combination of TRIM24 interference and chemotherapy is expected to improve the therapeutic effect of glioblastoma.
6. TRIM24 regulates the expression of drug resistance gene MGMT through PI3K/Akt/NF- kappa B signal transduction.
As DNA repair enzyme MGMT plays a key role in the drug resistance of temozolomide, we detected the effect of TRIM24 interference on the mRNA and protein levels of MGMT. The.Western blot experiment found that TRIM24 interference resulted in the decrease of MGMT protein content in T98 cells and.Real-time RT-PCR experiment showed that the interference was at the transcriptional level. Although the ChIP experiment did not see the TRIM24 binding MGMT gene promoter, the double luciferase reporter gene detection found that the TRIM24 interference caused the decrease of NF- kappa B transcriptional activity, that is, the effect of the inhibition of PI3K/Akt signal transduction is similar to that the effect of.TRIM24 interference on MGMT expression can be reversed by the reintroduced TRIM24, but if siRNA interferes with N The expression of the encoding gene RelA of the F- kappa B subunit p65 and the recovery of the MGMT level were blocked. These results suggest that the regulation of TRIM24 on MGMT expression is (or at least partly) mediated by the PI3K/Akt/NF- kappa B pathway.

【學位授予單位】：第四軍醫(yī)大學
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R739.41

【共引文獻】

相關期刊論文 前10條

1 金晶;王龍勝;;病案點評[J];安徽醫(yī)學;2009年12期

2 ;Platelet-derived growth factor receptor alpha in glioma:a bad seed[J];癌癥;2011年09期

3 謝云鵬;田甜;申興斌;王維興;錢濤;;星形細胞瘤組織TGF-β1、Smad7與VEGF的表達及意義[J];承德醫(yī)學院學報;2011年01期

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5 劉新新;韓曉雨;李智勇;苗延巍;;側(cè)腦室內(nèi)未成熟畸胎瘤1例MRI分析[J];磁共振成像;2010年06期

6 王斐斐;程敬亮;趙藝蕾;張勇;閆晨宇;白潔;張會霞;崔曉琳;;動態(tài)磁敏感對比MR灌注成像對腦膜瘤分級的臨床價值[J];磁共振成像;2011年01期

7 宋茜;齊悅彤;李瑩;;第三腦室脊索樣膠質(zhì)瘤1例[J];磁共振成像;2011年02期

8 劉才保;康厚藝;周鵬程;肖華亮;張偉國;;椎管內(nèi)彌漫性黑色素細胞增生癥1例[J];磁共振成像;2011年06期

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10 ;Gliomatosis Cerebri[J];Chinese Journal of Clinical Oncology;2008年04期

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