神经胶质瘤中microRNA的研究进展

近年来神经胶质瘤的治疗正寻找新的途径,研究发现非编码小RNA(microRNA,miRNA)参与了与肿瘤相关的所有过程,包括增殖、凋亡、转移、血管生成、免疫应答等,通过抑制信号网络中特定分子表达,发挥促癌或抑癌作用;某些miRNA可以分泌至外周血血清参与循环,这些为神经胶质瘤分子靶向治疗及诊断预后提供基础.本文就近几年来神经胶质瘤中新发现的、且报道较多的miRNA进行综述.     

微RNA与神经胶质瘤的关系

近来研究表明,某些微RNA(microRNAs,miRNA)在不同组织分型的胶质瘤中呈特异性表达,通过上调或下调相应的miRNA可诱导胶质瘤细胞的凋亡或抑制其增殖。应用微阵列技术分析不同胶质瘤中miRNA表达谱将有助于进一步探讨胶质瘤发生发展的机制,实现胶质瘤的个性化诊断,探索miRNA为靶点的胶质瘤基因治疗的可行性。     

微RNA与神经胶质瘤的关系

近来研究表明,某些微RNA（microRNAs,miRNA）在不同组织分型的胶质瘤中呈特异性表达,通过上调或下调相应的miRNA可诱导胶质瘤细胞的凋亡或抑制其增殖。应用微阵列技术分析不同胶质瘤中miRNA表达谱将有助于进一步探讨胶质瘤发生发展的机制,实现胶质瘤的个性化诊断,探索miRNA为靶点的胶质瘤基因治疗的可行性。     

微小RNA与胶质瘤干细胞放化疗敏感性

微小RNA（miRNA）的表达与胶质瘤干细胞对放疗及化疗的敏感程度密切相关。许多研究发现,调节单一miRNA能起到提高胶质瘤干细胞的放化疗敏感性、增加细胞凋亡、多方面综合抑制胶质瘤干细胞生长的效果。胶质瘤的治疗策略有望以miRNA为靶点,通过调节miRNA在细胞中的表达,从而达到提高胶质瘤干细胞放化疗敏感性的目的。     

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.     

神经生长因子及其受体与神经系统肿瘤的关系

研究表明神经生长因子(NGF)及其高亲和力受体酪氨酸激酶受体(TrkA)在神经系统肿瘤中表达发生改变,并且NGF及TrkA的高表达预示着神经母细胞瘤(NB)和髓母细胞瘤(MB)的良好预后,而在胶质瘤,NGF及TrkA的高表达和核转位与肿瘤的恶性程度密切相关.研究NGF及TrkA在神经系统肿瘤中的表达及亚细胞定位将为肿瘤的诊疗开辟新途径.     

NF-κB信号转导通路对神经胶质瘤生物学特性的影响及机制

核转录因子-κB（NF-κB）信号转导通路广泛存在于真核生物中,参与胚胎发育、炎症、免疫以及肿瘤的发生发展等多种生物进程。NF-κB 信号转导通路的异常激活与神经胶质瘤的生物学特性改变密切相关。研究 NF-κB 信号转导通路与胶质瘤增殖、侵袭、凋亡和血管新生的关系,将为神经胶质瘤的治疗提供新的思路和靶点。     

miR-451与造血细胞分化和肿瘤相关性的研究进展

miRNA是广泛存在于真核生物的一种内源性的小分子RNA,作为一种关键因素与肿瘤的发生、发展及细胞分化密切相关。miR-451在造血细胞成熟分化及维持红细胞稳定中起着关键的调控作用,并在胶质瘤、胃肠癌、肺癌等多种肿瘤组织中明显低表达。上调miR-451可以显著抑制肿瘤细胞的增殖、侵袭和转移,增加肿瘤细胞的凋亡率,提高肿瘤放、化疗敏感性等诸多生物学效应。本文对miR-451与造血细胞分化及肿瘤发生发展的相关研究进展作一综述。     

钠钾氯共转运体1与胶质瘤

钠钾氯共转运体1（NKCC1）在恶性胶质瘤中高表达,其与胶质瘤的恶性程度密切相关。NKCC1蛋白在胶质瘤细胞的体积调节方面起重要作用,NKCC1蛋白使胶质瘤细胞自如地变换体积,穿过狭窄的细胞外间隙向远处迁移播散;NKCC1与肿瘤细胞骨架调节也有密切关系。此外,NKCC1亦与细胞周期、神经能活性等其他生物功能密切相关。总之,NKCC1在胶质瘤中扮演了重要的角色。     

微小RNA与结直肠癌

微小RNA （miRNA）在细胞生长、分化、凋亡和肿瘤发生中发挥重要的调控作用.研究显示,miRNA调控目的基因表达与结直肠癌的发生发展、化疗敏感性及预后密切相关.检测miRNA有望为结直肠癌患者制定更详细的个体化化疗方案,并改善其预后.     

MicroRNA sequence and expression analysis in breast tumors by deep sequencing

MicroRNAs (miRNA) regulate many genes critical for tumorigenesis. We profiled miRNAs from 11 normal breast tissues, 17 noninvasive, 151 invasive breast carcinomas, and 6 cell lines by in-house-developed barcoded Solexa sequencing. miRNAs were organized in genomic clusters representing promoter-controlled miRNA expression and sequence families representing seed sequence-dependent miRNA target regulation. Unsupervised clustering of samples by miRNA sequence families best reflected the clustering based on mRNA expression available for this sample set. Clustering and comparative analysis of miRNA read frequencies showed that normal breast samples were separated from most noninvasive ductal carcinoma in situ and invasive carcinomas by increased miR-21 (the most abundant miRNA in carcinomas) and multiple decreased miRNA families (including miR-98/let-7), with most miRNA changes apparent already in the noninvasive carcinomas. In addition, patients that went on to develop metastasis showed increased expression of mir-423, and triple-negative breast carcinomas were most distinct from other tumor subtypes due to upregulation of the mir~17-92 cluster. However, absolute miRNA levels between normal breast and carcinomas did not reveal any significant differences. We also discovered two polymorphic nucleotide variations among the more abundant miRNAs miR-181a (T19G) and miR-185 (T16G), but we did not identify nucleotide variations expected for classical tumor suppressor function associated with miRNAs. The differentiation of tumor subtypes and prediction of metastasis based on miRNA levels is statistically possible but is not driven by deregulation of abundant miRNAs, implicating far fewer miRNAs in tumorigenic processes than previously suggested.     

循环微小RNA及其在结直肠癌中的研究

 在结直肠癌中已经发现多种微小RNA（miRNA）表达异常,推测其可能参与肿瘤发生发展过程。近年来越来越多的证据表明,miRNA比mRNA更稳定地存在于血液中,使循环miRNA有望成为一种非侵入性的可以指导结直肠癌诊断、治疗以及预后评价的肿瘤标志物。     

circRNAs在肿瘤中的研究进展

环状RNA（circular RNA, circRNA）是一种共价闭合的单股环状分子,属于非编码RNA家族成员。circRNA以保守、稳定、特异、高含量为特点,可作为microRNA海绵调控靶miRNA的活性,并参与基因转录和蛋白生成的调控,逐渐成为非编码RNA调控网络的新星。circRNA在多种疾病的发生发展中发挥重要作用,并且在肿瘤诊断、治疗和预后等方面具有巨大的潜能,有望成为新的肿瘤生物标志物或分子靶向治疗靶点。     

microRNA及其在淋巴瘤中的表达

 micro RNA（miRNA）是一类长度大约为22 nt的非编码小片段RNA，其进化保守，通过与mRNA的3'UTR相互作用进而调控mRNA的翻译，广泛作用于发育、炎症、凋亡和肿瘤等各个生物学过程。在T淋巴瘤中发现miR-106a和miR-17-92过度表达；在弥漫性大B细胞淋巴瘤和滤泡细胞淋巴瘤中的miR-155，miR-221和miR-21表达上调，并与肿瘤的亚型有关。miR-17 簇过度表达可使凋亡水平下降，表明这些miRNA的主要作用是抑制细胞的死亡。miRNA既可促进肿瘤的发生，又能抑制肿瘤，但其确切机制尚不明。随着研究的深入，miRNA的遗传表型调节功能将会越来越清楚。     

Development of miRNA‐based therapeutic approaches for cancer patients

Over the past few decades, siRNA and miRNA have attracted a great deal of attention from researchers and clinicians. These molecules have been extensively studied from the standpoint of developing biopharmaceuticals against various diseases, including heart disease, diabetes and cancers. siRNA suppresses only a single target, whereas each miRNA regulates the expression of multiple target genes. More importantly, because miRNA are also secreted from cancer cells, and their aberrant expression is associated with tumor development and progression, they represent not only therapeutic targets but also promising biomarkers for diagnosis and prognosis. Therefore, miRNA may be more effective tools against cancers, in which multiple signal pathways are dysregulated. In this review, we summarize recent progress in the development of miRNA therapeutics for the treatment of cancer patients, and describe delivery systems for oligonucleotide therapeutics.     

肿瘤相关微小RNA与凋亡

微小RNA(miRNA) 在转录后水平调控基因的表达.研究证实miRNA通过调控细胞的凋亡,在肿瘤的发生发展过程中发挥着重要的作用.肿瘤相关miRNA与凋亡的研究在未来的肿瘤诊疗中miRNA可能具有广阔的应用前景.     

Circulating miRNAs are correlated with tumor progression in prostate cancer

Circulating miRNAs have recently been indicated as practicable and promising biomarkers for noninvasive diagnosis in various tumor entities. However, cell‐free miRNAs have not been found to correlate with clinicopathological variables in epithelial carcinomas. To learn more about the potential clinical relevance of circulating miRNAs in prostate cancer, we screened 667 miRNAs in serum samples from patients with metastatic (n = 7) and localized prostate cancer (n = 14). Various miRNAs were highly abundant in the sera of patients with metastatic disease, and five upregulated miRNAs (miRNA‐375, miRNA‐9*, miRNA‐141, miRNA‐200b and miRNA‐516a‐3p) were selected for further validation. In the first validation study (n = 45), selected miRNAs were analyzed in a prospectively collected serum set taken from different prostate cancer risk groups. Most of the selected miRNAs were significantly correlated with adverse risk factors when different clinicopathological variables were analyzed. Circulating miRNA‐375 and miRNA‐141 turned out to be the most pronounced markers for high‐risk tumors. Their levels also correlated with high Gleason score or lymph‐node positive status in a second independent validation study (n = 71). In addition, the expression levels of miRNA‐375 and miRNA‐141 were monitored in 72 prostate tissue samples (36 tumor vs. 36 benign). Both miRNAs were highly expressed in all samples and significantly upregulated in the tumors compared to normal tissues. Overall, our observations suggest that miRNA‐375 and miRNA‐141 expression is enhanced in prostate cancer specimens and their release into the blood is further associated with advanced cancer disease.     

微小RNA与肿瘤血管生成

 肿瘤细胞表达的相关微小RNA（miRNA）通过调控血管内皮生长因子（VEGF）的表达,影响肿瘤血管生成,而血管生成在肿瘤的生长发展等过程中起着十分重要的作用。因此深入研究miRNA的功能将为抑制肿瘤血管生成提供更有效的靶点,为肿瘤的临床诊治提供更可靠的依据。     

外泌体在白血病中的研究进展

外泌体（exosomes，Exs）是多种细胞在正常及病理状态下均能分泌的微小囊泡，直径约40~100 nm，外泌体包含了丰富的蛋白质、miRNA以及RNA片段。近几年的研究表明外泌体可参与白血病的发生发展，在白血病的诊断和治疗中发挥作用。外泌体可通过影响细胞增殖、凋亡和自噬，调节骨髓微环境，促进血管生成及抑制骨髓造血等多方面促进白血病的发生发展。外泌体还可作为白血病的生物标志物，作为白血病的治疗靶点以及影响白血病耐药等。本文就外泌体的形成、组成和功能及近年来外泌体在白血病中的作用进行综述。