三结构域蛋白26在胶质瘤组织中的表达及临床意义

doi:10.6040/j.issn.1671-7554.0.2018.924

摘要/Abstract

摘要： 目的探讨三结构域蛋白26(TRIM26)在人脑胶质瘤组织中的表达,分析TRIM26的表达水平与患者临床病理特征之间的关系,并研究TRIM26过表达对人脑胶质瘤细胞系U87和U251增殖的影响。方法收集32例患者的胶质瘤组织及8例脑外伤患者内减压术中切除的脑组织(正常脑组织),采用实时定量PCR及免疫组化检测TRIM26mRNA及蛋白在胶质瘤组织和正常脑组织中的表达水平,并分析胶质瘤组织中TRIM26 mRNA表达水平与患者临床病理特征之间的相关性,Kaplan-Meier生存分析TRIM26mRNA表达水平与胶质瘤患者总生存时间、无复发生存时间之间的关系。MTT法检测TRIM26过表达对人脑胶质瘤细胞系U87及U251增殖的影响。结果免疫组化结果显示,TRIM26在胶质瘤组织中的表达量高于正常脑组织;实时定量PCR结果显示,TRIM26 mRNA在胶质瘤组织中表达量(3.51±0.92)高于正常脑组织(1.99±0.45)(P<0.01),Ⅲ-Ⅳ级胶质瘤中TRIM26的表达量(3.75±0.84)高于Ⅰ-Ⅱ级(2.65±0.62)(P<0.01)。胶质瘤组织中TRIM26的表达水平与患者胶质瘤病理级别显著相关(P=0.01),而与患者性别(P=0.72)、年龄(P=0.72)及异柠檬酸脱氢酶1(IDH1)突变(P>0.999)无显著相关。高表达TRIM26的胶质瘤患者总生存时间［(16.29±1.82)vs(28.73±1.41)个月,P<0.01］及无复发生存时间［(8.34±1.78 )vs(15.95±1.83)个月,P<0.01］低于低表达组。过表达TRIM26促进胶质瘤细胞U87及U251的增殖。结论 TRIM26在胶质瘤组织中呈高表达,并与患者病理级别和预后相关。

关键词: 三结构域蛋白26, 胶质瘤, 病理特征, 预后, 增殖

Abstract: Objective To detect the expression of tripartite motif protein 26(TRIM26)in glioma tissues, to analyze the relationship of its expression and multiple pathological parameters, and to explore the effect on its overexpression in U87 and U251 for the proliferation of glioma cells. Methods A total of 32 cases of glioma tissues and 8 cases of normal brain tissues were collected. Real-time quantitative PCR and immunohistochemistry were used to detect the expression of TRIM26 in levels of mRNA and protein. The relationship between TRIM26 mRNA expression and clinical pathological parameters was analyzed. Effect on TRIM26 overexpression in U87 and U251 for proliferation of glioma cells was detected by MTT assay. Results Immunochemistry results showed that the percentage of TRIM26 positive cells was higher in glioma tissues than control tissues. Compared with the control group, the expression of TRIM26 in glioma tissues was significantly increased ［3.51±0.92 vs 1.99±0.45, P<0.01］. The expression of TRIM26 in patients of Ⅲ-Ⅳ grade was markedly higher than in patients of Ⅰ-Ⅱ grade ［3.75±0.84 vs 2.65±0.62, P<0.01］. TRIM26 expression was observably associated with stage(P=0.01), but not gender(P=0.72), age(P=0.72), and IDH1 mutation(P>0.999). Moreover, Kaplan-Meier analysis demonstrated that increasing of TRIM26 expression contributed to shorter overall survival ［(16.29±1.82)vs(28.73±1.41)months, P<0.01］ and recurrence-free survival time ［(8.33±1.78)vs(15.95±1.83)months, P<0.01］. Overexpression of TRIM26 in U87 and U251 cell lines promoted the proliferation of glioma cells. Conclusion TRIM26 is highly expressed in glioma, and the overexpression of TRIM26 is associated with pathological grade and prognosis.

Key words: Tripartite motif protein 26, Glioma, Pathological parameters, Prognosis, Proliferation

中图分类号:

R739.41

赵学英,樊明德,董文艳,亓颖芝,芦鑫. 三结构域蛋白26在胶质瘤组织中的表达及临床意义[J]. 山东大学学报 (医学版), 2019, 57(3): 63-68.

ZHAO Xueying, FAN Mingde, DONG Wenyan, QI Yingzhi, LU Xin. Expression and clinical significance of tripartite motif protein 26 in glioma tissues[J]. Journal of Shandong University (Health Sciences), 2019, 57(3): 63-68.

参考文献

[1] Riddick G, Fine HA. Integration and analysis of genome-scale data from gliomas[J]. Nat Rev Neurol, 2011, 7(8):439-450.
[2] Gokden M. If it is not a glioblastoma, then what is it? a differential diagnostic review[J]. Adv Anat Pathol, 2017, 24(6):379-391.
[3] Goods BA, Hernandez AL, Lowther DE, et al. Functional differences between PD-1+ and PD-1- CD4+ effector T cells in healthy donors and patients with glioblastoma multiforme[J]. PLoS One, 2017, 12(9):e0181538. doi:10.1371/journal.pone.0181538.
[4] Dagogo-Jack I, Shaw AT. Tumour heterogeneity and resistance to cancer therapies[J]. Nat Rev Clin Oncol, 2018, 15(2):81-94.
[5] Wang Y, He D, Yang L, et al. TRIM26 functions as a novel tumor suppressor of hepatocellular carcinoma and its downregulation contributes to worse prognosis[J]. Biochem Biophys Res Commun, 2015, 463(3):458-465.
[6] Sanchez JG, Okreglicka K, Chandrasekaran V, et al. The tripartite motif coiled-coil is an elongated antiparallel hairpin dimer[J]. Proc Natl Acad Sci USA, 2014, 111(7):2494-2499.
[7] Tocchini C, Ciosk R. TRIM-NHL proteins in development and disease[J]. Semin Cell Dev Biol, 2015, 47-48:52-59. doi:10.1016/j.semcdb.2015.10.017.
[8] Uchil PD, Hinz A, Siegel S, et al. TRIM protein-mediated regulation of inflammatory and innate immune signaling and its association with antiretroviral activity[J]. J Virol, 2013, 87(1):257-272.
[9] Wu XL, Anderson JL, Campbell EM, et al. Proteasome inhibitors uncouple rhesus TRIM5alpha restriction of HIV-1 reverse transcription and infection[J]. Proc Natl Acad Sci USA, 2006, 103(19):7465-7470.
[10] Tocchini C, Keusch JJ, Miller SB, et al. The TRIM-NHL protein LIN-41 controls the onset of developmental plasticity in Caenorhabditis elegans[J]. PLoS Genet, 2014, 10(8):e1004533. doi:10.1371/journal.pgen.1004533.
[11] Li HY, Sun LL, Tang ZP, et al. Overexpression of TRIM24 correlates with tumor progression in non-small cell lung cancer[J]. PLoS One, 2012, 7(5):e37657. doi:10.1371/journal.pone.0037657.
[12] Zaman MM, Nomura T, Takagi T, et al. Ubiquitination-deubiquitination by the TRIM27-USP7 complex regulates tumor necrosis factor alpha-induced apoptosis[J]. Mol Cell Biol, 2013, 33(24):4971-4984.
[13] 王雨涛, 周济, 杨冬, 等. TRIM29基因在胶质瘤中的表达及其对胶质母细胞瘤细胞U-87 MG增殖与迁移的影响[J]. 第三军医大学学报, 2018, 40(11):959-965. WANG Yutao, ZHOU Ji, YANG Dong, et al. Expression of TRIM29 in gliomas and its effect on proliferation and migration of glioblastoma U-87 MG cells[J]. Journal of Third Military Medical University, 2018, 40(11):959-965.
[14] 龙璐, 王堃, 陈贞, 等. 三结构域包含蛋白29对鼻咽癌细胞生长和迁移的影响[J]. 中国现代医学杂志, 2015, 25(2):7-12. LONG Lu, WANG Kun, CHEN Zhen, et al. Effects of TRIM 29 on growth and migration of nasopharyngeal carcinoma cells[J]. China Journal of Modern Medicine, 2015, 25(2):7-12.
[15] Zhou XM, Sun R, Luo DH, et al. Upregulated TRIM29 promotes proliferation and metastasis of nasopharyngeal carcinoma via PTEN/AKT/mTOR signal pathway[J]. Oncotarget, 2016, 7(12):13634-13650.
[16] Xu R, Hu JY, Zhang TS, et al. TRIM29 overexpression is associated with poor prognosis and promotes tumor progression by activating Wnt/β-catenin pathway in cervical cancer[J]. Oncotarget, 2016, 7(19):28579-28591.
[17] Liu J, Welm B, Boucher KM, et al. TRIM29 functions as a tumor suppressor in nontumorigenic breast cells and invasive ER+ breast cancer[J]. Am J Pathol, 2012, 180(2):839-847.
[18] Ran Y, Zhang J, Liu LL, et al. Autoubiquitination of TRIM26 links TBK1 to NEMO in RLR-mediated innate antiviral immune response[J]. J Mol Cell Biol, 2016, 8(1):31-43.
[19] Nakagawa T, Hosogane M, Nakagawa M, et al. Transforming growth factor β-induced proliferative arrest mediated by TRIM26-dependent TAF7 degradation and its antagonism by MYC[J]. Mol Cell Biol, 2017, 38(5):e00449-17. doi:10.1128/mcb.00449-17.
[20] Zhao W, Li QT, Ayers S, et al. Jmjd3 inhibits reprogramming by upregulating expression of INK4a/Arf and targeting PHF20 for ubiquitination[J]. Cell, 2013, 152(5):1037-1050.
[21] Wang P, Zhao W, Zhao K, et al. TRIM26 negatively regulates interferon-β production and antiviral response through polyubiquitination and degradation of nuclear IRF3[J]. PLoS Pathog, 2015, 11(3):e1004726. doi:10.1371/journal.ppat.1004726.
[22] Lee JS, Bae JS, Kim JH, et al. Association study between TRIM26 polymorphisms and risk of aspirin-exacerbated respiratory disease[J]. Int J Mol Med, 2012, 29(5):927-933.
[23] Abdel-Mohsen M, Raposo RA, Deng XT, et al. Expression profile of host restriction factors in HIV-1 elite controllers[J]. Retrovirology, 2013, 10:106. doi:10.1186/1742-4690-10-106.
[24] de Jong S, van Eijk KR, Zeegers DW, et al. Expression QTL analysis of top loci from GWAS meta-analysis highlights additional schizophrenia candidate genes[J]. Eur J Hum Genet, 2012, 20(9):1004-1008.
[25] Lyu XM, Zhu XW, Zhao ML, et al. A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response[J]. Cancer Med, 2018, 7(8):3848-3861.
[26] Zhang JD, Zhang CX, Cui J, et al. TRIM45 functions as a tumor suppressor in the brain via its E3 ligase activity by stabilizing p53 through K63-linked ubiquitination[J]. Cell DeathDis, 2017, 8(5):e2831. doi:10.1038/cddis.2017.149.
[27] Guo PB, Qiu YM, Ma XM, et al. Tripartite motif 31 promotes resistance to anoikis of hepatocarcinoma cells through regulation of p53-AMPK axis[J]. Exp Cell Res, 2018, 368(1):59-66.
[28] Liu JJ, Rao J, Lou XM, et al. Upregulated TRIM11 exerts its oncogenic effects in hepatocellular carcinoma through inhibition of P53[J]. Cell Physiol Biochem, 2017, 44(1):255-266.
[29] Yuan ZG, Villagra A, Peng LR, et al. The ATDC(TRIM29)protein binds p53 and antagonizes p53-mediated functions[J]. Mol Cell Biol, 2010, 30(12):3004-3015.
[30] Liu J, Zhang C, Feng Z,et al.E3 ubiquitin ligase TRIM32 negatively regulates tumor suppressor p53 to promote tumorigenesis[J]. Cell Death Differ, 2014, 21(11):1792-804.

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