脑胶质瘤组织中微小RNA 21水平及其与EGFR和VEGF表达的关系#br# #br#

目的探讨脑胶质瘤组织中微小RNA 21（miR 21）水平及其与表皮生长因子受体（EGFR）和血管内皮生长因子（VEGF）表达的关系。 方法选取本院2005年1月至2015年6月手术切除并经病理证实的WHO Ⅲ、Ⅳ级脑胶质瘤组织92例,另取50例癌旁组织作对照。采用实时荧光定量PCR（QPCR）检测以上组织中的miR 21水平,免疫组化检测EGFR和VEGF表达,分析脑胶质瘤组织中miR 21水平与临床病理参数（性别、年龄、民族和病理分级）及EGFR和VEGF表达的关系,Spearman等级相关分析miR 21水平与EGFR和VEGF表达的相关性。 结果QPCR检测结果显示脑胶质瘤组织中miR 21水平为1307±769,高于癌旁组织,差异有统计学意义（P＜005）;miR 21水平与性别、年龄及民族无关（P＞005）,仅与病理分级有关（P＜005）,其中Ⅳ级的miR 21水平为16483±4980,高于Ⅲ级的3229±3165,差异有统计学意义（P＜005）。EGFR和VEGF阳性表达率均为870％（80／92）,其中EGFR阳性表达者的miR 21水平为13952±8062,高于阴性表达者的3487±3309（P＜005）,而VEGF阳性表达者的miR 21水平为13874±8340,高于阴性表达者的2090±1458（P＜005）;Spearman等级相关分析发现脑胶质瘤组织中miR 21水平与EGFR、VEGF表达均呈正相关（r=0251、0311, P＜005）。 结论脑胶质瘤组织中miR 21水平升高,且与病理分级和EGFR、VEGF表达有关,可能参与了该恶性肿瘤的发生发展,对脑胶质瘤的诊治有一定临床意义。     

miR-181家族的表达与人脑胶质瘤恶性程度的关系

目的：探讨miR-181家族，miR-181a、miR-181b和miR-181c，在不同恶性程度的人脑胶质瘤中的表达。方法：收集病理确诊的15例不同恶性程度胶质瘤以及5例正常脑组织手术标本，提取总微小RNA，应用实时荧光定量PCR技术检测miR-181a、miR-181b和miR-181c基因在人脑胶质瘤组织和正常脑组织中的表达，并进一步比较miR-181家族表达情况与不同级别胶质瘤的相关性。结果：miR-181a和miR-181b，在人脑不同级别胶质瘤中表达均明显下降。miR—18Ia表达水平呈随胶质瘤级别增高而下降趋势。miR-181b在胶质瘤级别HI级以上表达水平趋于稳定，Ⅲ级和Ⅳ级组织中的表达无明显差异。miR-181c表达量在正常脑组织与胶质瘤Ⅱ级和Ⅲ级组织间差异不显著．在胶质瘤Ⅳ级组织miR—181c表达水平降低。结论：miR-181a、miR-181b和miR-181c在胶质瘤组织中呈不同程度低表达，miR-181a表达与胶质瘤级别呈负相关，     

胶质瘤耐药相关因素的研究进展

胶质瘤耐药现象的存在是胶质瘤化疗效果不佳的重要原因。对其耐药分子机制的研究是当前的热点和难点。研究发现胶质瘤耐药的分子机制异常复杂．胶质瘤肿瘤细胞内耐药基因及其相关蛋白的异常表达,脑肿瘤干细胞与多药耐药以及DNA损伤修复能力的异常与耐药密切相关,本文对胶质瘤这些耐药的分子机制和相关因素进行了综述。     

survivin、cyclin b1在人脑胶质瘤的表达及意义

 目的　探讨survivin基因在人脑胶质瘤中的表达及其与cyclinb1蛋白表达的相关性。方法　采用免疫组织化学SABC法检测survivin、cyclinb1表达蛋白在 4 1例胶质瘤 10例正常脑组织中的表达。结果　survivin基因表达蛋白在正常脑组织中无表达 ;4 1例胶质瘤中 2 5例呈阳性表达 ,占 6 1.0 %。Ⅰ～Ⅱ级和Ⅲ～Ⅳ级间的表达有显著性差异 (P <0 .0 5 )。胶质瘤组织survivin蛋白的表达与cyclinb1蛋白表达密切相关 (rs=0 .836 ,P <0 .0 1)。结论　survivin蛋白异常表达在胶质瘤的发生中起重要作用 ,它可能与cyclinb1共同在胶质瘤细胞有丝分裂的Gs2 /M期中起特殊促进作用。     

Survivin、MVD在人脑胶质瘤中的表达及意义

目的　探讨Survivin基因在人脑胶质瘤中的表达 ,及其与MVD的相关性。方法　采用免疫组织化学SABC法检测Survivin、CD34在 4 1例胶质瘤及 10例正常脑组织中的表达。结果　Survivin蛋白在正常脑组织中无表达 ,4 1例胶质瘤中 ,2 5例呈阳性表达 ,占 6 1 0 % ,Ⅰ～Ⅱ级和Ⅲ～Ⅳ级间的表达有显著性差异P<0 .0 5 ) ;胶质瘤组织中Survivin蛋白的表达与MVD的表达密切相关P <0 .0 1,rs=0 .70 7)。结论　Survivin蛋白异常表达在胶质瘤的恶化中起重要作用 ,它可能促进血管内皮细胞的增生 ,从而促进肿瘤细胞的增殖     

应用组织芯片技术研究HDAC6在胶质瘤组织中的表达及预后意义

目的:探讨胶质瘤组织中HDAC6的表达及其与临床病理资料之间的关系.方法:采用免疫组化法检测胶质瘤组织芯片(正常脑组织20例、癌旁组织27例、胶质瘤组织206例)中HDAC6的表达量及其与临床病理资料之间的关系,应用SPSS 16.0软件分析胶质瘤组织中HDAC6表达水平与胶质瘤临床病理之间的相关性及其对胶质瘤患者预后的影响.结果:HDAC6在胶质瘤中的表达量明显高于正常脑组织和癌旁组织(P<0.05),并且在高级别胶质瘤(III-IV)中的蛋白表达量明显高于低级别胶质瘤(I-II)中的蛋白表达量.依据生存分析,发现HDAC6蛋白在低表达组中与高表达组相比有生存优势,PFS(无进展生存期)及OS(总生存期)均延长,差异具有统计学意义(P<0.05).结论:HDAC6在胶质瘤中的表达量明显升高,促进了肿瘤的发生和发展,通过HDAC6表达水平可预测胶质瘤患者的预后.     

人脑胶质细胞瘤中血管内皮生长因子基因的表达研究

目的　研究血管内皮生长因子 (vascularendothelialgrowthfactor ,VEGF)在脑胶质细胞瘤中的表达及其与肿瘤病理分级、新生血管形成的关系。方法　采用Northern杂交和免疫组织化学染色检测 3 0例脑胶质瘤标本 ,2例脑胶质瘤细胞株 ,4例正常脑组织的VEGFmRNA和蛋白表达水平。结果　正常脑组织中VEGFmRNA的表达水平极低 ,而脑胶质瘤组织和细胞系中VEGFmRNA的表达水平高 ,P <0 .0 5。在正常脑组织中未见VEGF免疫组化染色阳性细胞 ,脑胶质瘤组织和细胞系中VEGF高表达 ,P <0 .0 5。随着脑胶质瘤恶性程度的增加 ,VEGFmRNA的表达增高 (γ =0 .85 ,P <0 .0 1)。VEGF的表达还与肿瘤的血管密度相关 (γ =0 .88,P <0 .0 1)。结论　脑胶质瘤中VEGF的异常表达 ,是判断脑胶质细胞瘤恶性程度和血管丰富程度的 1项客观指标。     

FHL1A在胶质瘤组织中的表达及其与胶质瘤患者预后的关系

目的 探讨FHL1A在胶质瘤组织中的表达及其与胶质瘤患者预后的关系.方法 采用免疫组化法检测FHL1A在89例胶质瘤组织中的表达,同时采用该方法与western blot法对38例配对样本(同一患者的肿瘤组织及其周围正常组织)FHL1A表达差异进行检测,并对各病例的预后影响与FHL1A表达差异间关系进行分析比较.结果 FHL1A 在胶质瘤中表达明显低于其在周围正常组织中表达,且差异具有统计学意义(P＜0.05).同时FHL1A 的表达与胶质瘤级别呈负相关,FHL1A表达低的患者预后效果差.结论 FHL1A的表达与胶质瘤的预后及恶性程度密切相关,对临床诊断及预后判断有参考价值.     

Wnt/β-catenin信号转导途径异常在脑胶质瘤发生中的作用

Wnt/β-catenin信号转导途径与脑胶质瘤的发生发展密切相关.Wnt/β-catenin信号转导途径抑制因子及部分成员的异常表达能够促进胶质瘤细胞增殖,并抑制凋亡,从而导致胶质瘤的发生.研究Wnt/β-catenin信号转导途径与胶质瘤发生发展的关系可增进对胶质瘤发病机制的认识,并有望成为胶质瘤基因治疗的新靶点.     

SOX家族在脑胶质瘤中的表达及作用

脑胶质瘤是神经系统常见的恶性肿瘤.SOX家族的许多基因与脑胶质瘤的发生发展密切相关,其中SOX2、SOX4、SOX7、SOX9基因在脑胶质瘤中均有异常表达.SOX2基因在脑胶质瘤组织中高表达,与脑胶质瘤的恶性分级呈正相关,并且与众多因子协调促进脑胶质瘤的发生、发展;SOX4基因在脑胶质瘤中既是致癌基因又是抑癌基因,且能对多种因子进行调控;SOX7作为一种肿瘤抑制基因,在脑胶质瘤组织中低表达,通过调节相关因子及信号通路抑制脑胶质瘤的发生;SOX9基因在脑胶质瘤组织中高表达,与多种因子协调促进脑胶质瘤的发生及转移,是判断脑胶质瘤患者预后的重要因素.     

Circulating microRNAs in cancer: diagnostic and prognostic significance

The involvement of microRNAs (miRs) in numerous pathological conditions is well established. In many kinds of cancer cells and animal models, various miRs have been shown to act as oncogenes or tumor suppressors. Recently, it was found that circulating miRs can be detected, and may be associated, with the clinicopathological features and prognosis of cancers, thus, providing potential novel diagnostic and prognostic markers for malignancies in humans. This review aims to address these issues based on recently published literature.     

Changes in circulating microRNA levels associated with prostate cancer

Background:

The aim of this study was to investigate the hypothesis that changes in circulating microRNAs (miRs) represent potentially useful biomarkers for the diagnosis, staging and prediction of outcome in prostate cancer.

Methods:

Real-time polymerase chain reaction analysis of 742 miRs was performed using plasma-derived circulating microvesicles of 78 prostate cancer patients and 28 normal control individuals to identify differentially quantified miRs.

Results:

A total of 12 miRs were differentially quantified in prostate cancer patients compared with controls, including 9 in patients without metastases. In all, 11 miRs were present in significantly greater amounts in prostate cancer patients with metastases compared with those without metastases. The association of miR-141 and miR-375 with metastatic prostate cancer was confirmed using serum-derived exosomes and microvesicles in a separate cohort of patients with recurrent or non-recurrent disease following radical prostatectomy. An analysis of five selected miRs in urine samples found that miR-107 and miR-574-3p were quantified at significantly higher concentrations in the urine of men with prostate cancer compared with controls.

Conclusion:

These observations suggest that changes in miR concentration in prostate cancer patients may be identified by analysing various body fluids. Moreover, circulating miRs may be used to diagnose and stage prostate cancer.     

Serum micro-RNA Identifies Early Stage Colorectal Cancer in a Multi-Ethnic Population

Objective: Certain microRNAs (miR) have been previously described to be dysregulated in cancers and can be detected in blood samples. Studies examining the utility of miRs for colon cancer screening have primarily been performed in ethnically homogeneous groups of patients, thus the performance of miRs in multiethnic populations is unknown. Methods: Four miRs were selected that were shown to be aberrantly expressed in the blood or stool of patients with colorectal cancer (CRC) of various ethnicities. In this study, the ability of these miRs to discern early stage CRC was determined in a previously untested multiethnic population of 73 CRC cases and 18 controls. Results: The ratios of non-vesicular to extracellular vesicular levels of miR’s -21, -29a, and -92a were statistically and quantitatively related to CRC stage compared to controls. Conclusion: Serum levels of miR-21, miR-29a and miR-92a were able to significantly detect early stage CRC in a multiethnic and previously untested population.     

MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer

To define novel pathways that regulate susceptibility to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in non-small cell lung cancer (NSCLC), we have performed genome-wide expression profiling of microRNAs (miRs). We show that in TRAIL-resistant NSCLC cells, levels of different miRs are increased, and in particular, miR-221 and -222. We demonstrate that these miRs impair TRAIL-dependent apoptosis by inhibiting the expression of key functional proteins. Indeed, transfection with anti-miR-221 and -222 rendered CALU-1-resistant cells sensitive to TRAIL. Conversely, H460-sensitive cells treated with -221 and -222 pre-miRs become resistant to TRAIL. miR-221 and -222 target the 3'-UTR of Kit and p27(kip1) mRNAs, but interfere with TRAIL signaling mainly through p27(kip1). In conclusion, we show that high expression levels of miR-221 and -222 are needed to maintain the TRAIL-resistant phenotype, thus making these miRs as promising therapeutic targets or diagnostic tool for TRAIL resistance in NSCLC.     

Current Progress on Understanding MicroRNAs in Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is an aggressive grade IV astrocytoma with a 1-year median survival rate despite current treatment modalities. A thorough understanding of the vast genetic aberrations and signaling pathways involved in gliomagenesis as well as heterogeneous clinicopathological presentation remains elusive. The recent discovery of microRNAs (miRs) and their capability of simultaneously regulating multiple downstream genes may play a key role in explaining the complex mechanisms underlying GBM formation. miRs are 19 to 25 nucleotide non-protein-coding small RNA molecules involved in the suppression of mRNA translation. This review will summarize and discuss the most recent findings regarding miRs in GBM including downstream targets, functional effects, and therapeutic potentials. Specifically discussed miRs include miR-7, miR-9/miR-9*, miR-10a/miR-10a*/miR-10b, miR-15b, miR-17-92, miR-21, miR-26a, miR-34a, miR-93, miR-101, miR-124, miR-125a, miR-125b, miR-128, miR-137, miR-146b-5p, miR-153, miR-181a/miR-181b, miR-196a/miR-196b, miR-218, miR-221/miR-222, miR-296, miR-302-367, miR-326, miR-381, miR-451, and let-7a. In addition to gene regulatory roles, miRs have demonstrated significant diagnostic, prognostic, and therapeutic potential. These small molecules may both help in the understanding of GBM and in developing new therapeutic options.     

About the Cover北大核心CSCD

The cover art is an electron microscopy image illustrating chitosan nanoparticles carrying a microRNA (miR).One of the key issues in delivering miRs in vivo relates to nuclease mediated degradation before reaching target sites.These concerns call for a suitable delivery system,which will protect the naked miRs from nucleases in vivo.The ideal systemic delivery system for miRNA antagomirs or miRs is expected to provide robust target binding and will require a     

miR signatures and the role of miRs in acute myeloid leukaemia

Acute myeloid leukaemia (AML) is a hematopoietic stem cell disorder in which neoplastic myeloblasts are arrested in an immature stage of differentiation. Recent publications have underlined the involvement of non-coding RNAs in cancer and particularly in AML development, with several studies regarding their possible contribution to the evolution of the disease. MicroRNAs (miRs) are a class of single-stranded non-coding RNAs that bind to the 3′-untranslated region of target mRNAs and thus negatively regulate gene expression, by translation repression or mRNA degradation. Abnormal expression of miRs in AML has been described and we here review the current data from miR expression profiles. Additionally, we review the current knowledge on the biological function of individual miRs in the development of AML.