微小RNA与垂体腺瘤发病机制的相关研究进展

微小RNA(miRNA)作为一种新的遗传物质,是近年分子生物学研究的热点之一,其与肿瘤发病机制的研究越来越深入。miRNA是一类长度约21~25个核苷酸的内源性非编码RNA,主要与靶基因的3'非翻译区结合,并参与基因的转录后表达。而垂体腺瘤是一种常见颅内肿瘤,发病率仅次于胶质瘤、脑膜瘤,约占颅内肿瘤的15%。近年研究发现:miRNA参与垂体腺瘤的细胞增殖、分化、凋亡,与肿瘤发生、发展密切相关。本文主要介绍miRNA在垂体腺瘤发病机制中的研究进展。     

MicroRNA调控胶质瘤替莫唑胺化疗耐药的研究进展

microRNA是一类非编码的内源性小分子RNA,对基因表达进行转录后水平的调控。国内外学者对miRNA在胶质瘤耐药中的作用做了积极的探索和研究,发现miRNA在耐药中起十分重要的作用。本文将阐述miRNA与胶质瘤替莫唑胺化疗耐药基因的关系,促进在胶质瘤中针对特定通路的新靶向治疗的进一步发展。     

MicroRNA在脑胶质瘤临床应用中的研究进展

脑胶质瘤是成人最常见的颅内原发性肿瘤,其恶性程度高、易复发、预后差,一旦确诊,中位生存期很短。虽然目前在手术、化疗、放疗、免疫疗法及中医药等治疗上取得长足进步,但其大体预后仍未改善。近年来随着分子生物学的发展,一类长18~24个核苷酸的内源性非编码小分子RNA即microRNA(miRNA)引起了科学家的关注。miRNA可以通过调控靶基因从而改变靶蛋白的表达,其在脑胶质瘤的诊断、化疗药物疗效的评估、抗血管生成、治疗及预后判断等方面具有重要的临床意义。越来越多的研究发现,miRNA在脑胶质瘤发生、发展过程中发挥着重要的作用,可能作为今后脑胶质瘤临床诊断、预后评估的新指标及治疗的新靶点。本文将对miRNA在脑胶质瘤临床应用中的研究进展进行综述。     

微小分子RNA在胶质瘤中的研究进展

神经胶质瘤的治疗预后很差,胶质母细胞瘤中存在致肿瘤和抗细胞凋亡的特异性miRNA谱系.6个相互独立的表达谱研究确认了胶质瘤中28个上调的miR和33个下调的miR.其中miR-10b、miR-21和miR-221/222是胶质瘤中最主要的miRNA体系.miR-221和miR-222的过可以导致蛋白碱性磷酸酶μ(PTPμ)的下调,从而使得胶质瘤细胞的迁移率和生长率升高,并且p27、p57和PTEN都是miR-221和miR-222的作用靶点.同时miRNA的表达可能与GBM病人的生存期具有很强的关联.近年来研究表明miRNA可以在血液中稳定的存在,至于其存在的机制及对胶质瘤可能产生的影响,目前尚不确定.目前miRNAs作为肿瘤诊断分子标志物的作用已经在肿瘤研究领域中逐渐显现出来.未来随着对miRNA研究的深入,有可能为胶质瘤的治疗提供新的思路.     

miRNA调控脑胶质瘤癌基因表达研究进展

微小RNA（microRNA，miRNA）是一类长度为19—25个核苷酸的内源性非编码小RNA，在基因调节、细胞分化、机体发育中起着调控作用。脑胶质瘤是一种常见的原发性中枢系统肿瘤，而手术等传统疗法对其治疗效果不尽人意。近年来，随着研究的不断深入，miRNA表达调控的分子机制日益明了，为利用miRNA治疗胶质瘤提供了可能。癌基因在肿瘤细胞中的异常表达，是促进肿瘤发生发展的重要因素。     

DNA甲基化和miRNA在胶质瘤中的研究进展

DNA甲基化、微RNA（miRNA）在胶质瘤的发生、发展中起重要作用。多条癌症通路相关基因启动子区域的CpG岛甲基化发生频率与胶质瘤的发生与发展、组织类型和病理分级密切相关。miRNA的异常表达通过调控靶向基因、作用于癌症相关通路及脑肿瘤干细胞等机制扮演着抑癌或致癌角色。而miRNA的表达也受到甲基化的调控,这对综合评价肿瘤的发生、发展具有重要的意义。本文即对这两者在胶质瘤中的作用机制进行综述。     

微小RNA在胶质瘤对替莫唑胺耐药中的作用及机制研究进展

胶质瘤是中枢神经系统常见的恶性肿瘤,手术与放疗、化疗联合是主要治疗方案。替莫唑胺是一线化疗药物,可显著延长胶质瘤患者的生存时间。然而,胶质瘤的总体预后仍不理想,其中一个重要原因是存在肿瘤对替莫唑胺的耐药现象。研究表明胶质瘤对替莫唑胺产生耐药的影响因素包括DNA修复系统、细胞自噬、肿瘤干细胞、肿瘤微环境,等。微小RNA(miRNA)作为一类重要的转录后调控因子,可影响包括肿瘤化疗耐药在内的多项生物学行为。文中就近年来miRNA在胶质瘤对替莫唑胺耐药中的作用及机制研究进展做综述。     

p53及其调控基因在胶质瘤和脑肿瘤干细胞中的作用

胶质瘤是成人最常见的原发性脑肿瘤,抑癌基因p53突变在胶质瘤中十分常见,但其机制尚未明确.近期研究显示:P53蛋白能控制肿瘤干细胞的自我更新并抑制其多能性.与胶质瘤相关的p53调控因子Pict1、Nanog、Bcl2L 12以及miRNA 则可能为胶质瘤及其干细胞提供新的基因治疗靶点.活化脑肿瘤干细胞中的P53联合现行治疗方案可能成为胶质瘤有效的治疗方法.     

miR-137对U87胶质瘤细胞中EZH2表达和细胞增殖的影响

目的研究miR-137对U87胶质瘤细胞EZH2表达及细胞增殖的影响。方法先用双荧光素酶报告基因检测系统筛选靶向EZH2 3'-非翻译区(3'-UTR)的miRNA,然后采用逆转录聚合酶链反应(RT-PCR)和Western blot检测在胶质瘤细胞中作用最强的miRNA对EZH2 mRNA和蛋白表达的影响,再用MTT法检测该miRNA对U87胶质瘤细胞增殖的影响。结果胶质瘤细胞中低表达的9个miRNA被预测靶向EZH2的3'-UTR。双荧光素酶报告基因检测表明:miR-126、miR-137和miR-138能使荧光素酶活性显著降低,其中miR-137的作用最强(P<0.01)。RT-PCR和Western blot结果也显示miR-137能抑制EZH2 mRNA和蛋白的表达。MTT结果显示:miR-137能抑制U87胶质瘤细胞增殖,过表达EZH2基因可拮抗miR-137对胶质瘤细胞增殖的抑制作用。结论 miR-137可抑制U87胶质瘤细胞增殖,可能与抑制EZH2基因表达有关。     

人脑胶质瘤细胞系miRNA表达谱初步研究

目的 确定部分人脑胶质瘤细胞系miRNA表达谱的初步特征.方法 提取人脑胶质母细胞瘤细胞系U251、TJ861、TJ905、TJ899和A172以及星形细胞瘤细胞系H4细胞的miRNA,miRNA微阵列芯片杂交,扫描后分析差异表达的miRNA.选择差异表达的miR-21设计反义寡核苷酸处理U251细胞后原位杂交和Western blot检查SEPT 7的表达.结果 在胶质瘤细胞系中hsa-miR-21等8种miRNA一致表达上调;hsa-miR-1等18种miRNA一致表达下调.miR-21锁核酸修饰反义寡核苷酸处理U251细胞72h后,原位杂交发现阳性信号集中在细胞核的miR-21表达显著下降,Western blot发现U251细胞中SEPT 7的表达明显上调.结论 miRNA的差异表达可能是胶质瘤的重要分子生物学标签,并在基因表达调控中具有潜在的研究价值.     

Retinoic acid downregulates microRNAs to induce abnormal development of spinal cord in spina bifida rat model

Objects MicroRNAs have been found in the developing central nervous system, but little is known about their functions in development, especially in the abnormal development of spinal cord in spina bifida. To this end, we have studied the mechanism of microRNAs involved in the morphogenesis of the spinal cord in all-trans-retinoic acid (RA)-treated spina bifida rat fetus. Materials and methods Timed-pregnant rats were gavage-fed RA, and embryos were obtained on 13.5, 15.5, 17.5, and 19.5 days. MicroRNAs’ expression profile was analyzed by Northern blot. In situ apoptosis detection and microRNA in situ hybridization methods on sections of paraffin-embedded tissues were employed to explore the mechanism. Conclusion Administration of RA reduced the size of the spinal cord, probably as a consequence of increased cell death. There is a dramatic decrease in the expression of miR-9/9*, miR-124a and miR-125b, and Bcl2 and P53 as well in the sacral cord from E13.5 to E19.5 days post coitum. Our data showed that expression of these microRNAs was dysregulated in RA-treated spinal cord during embryonic development, suggesting that they may be involved in the development of the spinal cord.     

MicroRNA expression profiles and functions in the brain

MicroRNAs are abundant in the brains of vertebrates and some show a brain-specific or brain-enriched expression pattern. Because microRNAs regulate the expression of hundreds of target genes, it is not surprising that they have profoundly important functions in brain development and pathological processes. For example, miR-124 plays an important role in inducing and maintaining neuronal identity through targeting at least two anti-neural factors. MicroRNAs have also been implicated in brain disorders, including brain tumors and neurodegenerative diseases. This review aims to present an overview of the expression profiles and functions of microRNAs in the developing brains of vertebrates.     

MicroRNAs as potential therapeutics for treating spinal cord injury

MicroRNAs are a class of recently discovered,small non-coding RNAs that have been shown to play essential roles in a vast majority of biological processes.Very little is known about the role of microRNAs during spinal cord injury.This review summarizes the changes in expression levels of microRNAs after spinal cord injury.These aberrant changes suggest that microRNAs play an important role in inflammation,oxidative stress,apoptosis,glial scar formation and axonal regeneration.Given their small size and specificity of action,microRNAs could be potential therapeutics for treating spinal cord injury in the future.There are rapidly developing techniques for manipulating microRNA levels in animals;we review different chemical modification and delivery strategies.These may provide platforms for designing efficient microRNA delivery protocols for use in the clinic.