微小RNA与肿瘤

 相关研究发现在肿瘤患者的血液或尿液中,存在着相对特异的微小RNA（miRNA）表达谱,血液、尿液中的miRNA稳定性强、重复性好,可将其作为肿瘤早期诊断、个性化治疗、预后监测或跟踪随访的非创伤性生物标志物。     

诊断肿瘤新型标志物血清miRNA

 微小RNA(miRNA )功能失调与肿瘤的发生、发展密切相关。血清miRNA不仅具有良好的稳定性,而且有显著的肿瘤相关性和组织特异性。血清miRNA的检测具有获取简便、创伤小、技术快速等优点,因此可作为新的诊断肿瘤的分子标志物。     

miR-221和miR-222在肿瘤中的研究进展

 由于微小RNA(miRNA)在肿瘤中发挥重要调控作用及其自身特点,使其可能成为基因靶向治疗的有效工具。因此,人们致力于寻找调节关键癌基因或抑癌基因的miRNA。研究发现miR-221及miR-222在多种人类肿瘤中不仅表达异常,而且在不同类型的肿瘤中也发挥着不同的癌基因或抑癌基因样作用,通过调控miR-221和miR-222的表达可能成为肿瘤治疗的有效方法。     

白藜芦醇与肿瘤转移

 白藜芦醇是天然存在的一种植物抗生素,体内外实验表明,白藜芦醇能够通过影响基质金属蛋白酶及组织抑制剂的表达水平、抑制肿瘤血管的生成、干扰信号传导通路等多种途径抑制肿瘤转移。     

miR-19与肿瘤

 miR-17~92基因簇编码6种成熟的miRNA,包括miR-17、miR-20a、miR-18a、miR-19a、miR-19b和miR-92a-1,是一类典型的致癌多作用子miRNA。miR-19（包括miR-19a和miR-19b）是其中最重要的致癌miRNA,在淋巴瘤、白血病、肺癌、乳腺癌、多发性骨髓瘤等肿瘤中均表达上调,成为研究的热点之一。miR-19可通过抑制靶基因如PTEN、PP2A、Bim、SOCS1等促进肿瘤的增殖、侵袭和转移,与PI3K-AKT-mTOR信号转导通路关系密切,在肿瘤的发生发展中起着非常重要的作用。     

微小核糖核酸作为肿瘤标记物的研究

肿瘤标记物在临床诊断、治疗、预测预后方面发挥很重要的作用.而微小核糖核酸(miRNA)作为一种小分子RNA,在机体发挥的作用受到广泛认可,其中与肿瘤关系的研究得到了广泛的关注,尤其是作为肿瘤标记物指导临床诊疗方面.     

活化激酶C受体与肿瘤

 活化激酶C受体(RACK1)蛋白作为一种锚定蛋白,可以与细胞中多种信号分子结合,参与细胞内许多信号通路的传导。RACK1在肿瘤细胞信号转导分子网络中的作用受到了研究者的关注。大量研究揭示了肿瘤细胞中RACK1通过调节肿瘤血管形成和免疫逃逸,调节信号转导,并发挥重要的作用。     

微小RNA相关调控通路与肿瘤发生发展

 研究表明,微小RNA（miRNA）在多数肿瘤中存在异常表达。miRNA相关调控通路,包括miRNA与蛋白编码基因及miRNA与长链非编码RNA（lncRNA）间的相互调控,与肿瘤的发生发展密切相关。miRNA有望成为临床肿瘤治疗的新靶点。     

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。     

外周血miRNA作为肿瘤标志物的研究进展

miRNA是一类长度为20～24个核苷酸的非编码小分子RNA,与靶基因3'端非编码区不完全配对,从而抑制靶基因mRNA的翻译,影响个体发育、细胞凋亡、细胞增殖和分化等生命活动,与肿瘤的发生、转移和耐药等病理进程密切相关.近年来的研究发现,除了组织和细胞中的miRNA,外周血miRNA的表达也表现为显著的肿瘤相关性、组织特异性和表达稳定性,符合肿瘤标志物的要求.本文就外周血miRNA作为肿瘤标志物的研究进展进行综述.     

Analysis of miR-205 and miR-155 expression in the blood of breast cancer patients

The purpose of this study was to identify and validate circulating microRNAs (miRNAs) in human plasma for use as breast cancer (BC) biomarkers and to analyze their relationship to clinicopathologic features and its preliminary biological function. Genome-wide expression profiling of miRNAs in BC was investigated by microarray analysis. miR-155 was up-regulated greater than two-fold in BC compared with Normal Adjacent Tissue (NAT), whereas let-7b, miR-381, miR-10b, miR-125a-5p, miR-335, miR-205 and miR-145 were down- regulated greater than two-fold. Our hypothesis was that circulating miRNAs are also present and differentially expressed in the serum of BC patients compared to controls. Using real-time PCR (RT-PCR), we analyzed miR-205 and miR-155 in archived serum from 30 participants, 20 with breast cancer and 10 healthy people. miR-205 was down-regulated in BC patient serum while miR-155 was up-regulated. Furthermore, we analyzed the relationship between the expression levels of these two miRNAs and the clinicopathologic parameters of BC patients. High expression of miR155 was associated with clinical stage, molecular type, Ki-67 and p53 in BC patients (P<0.05). By contrast, we found no significant correlation between miR-205 and BC patient clinicopathologic parameters. Functional analysis showed that ectopic expression of miR-205 significantly inhibits cell proliferation and promotes apoptosis. miR-205 was down-regulated and miR-155 was up-regulated in BC patient serum. miR-155 was positive correlated with clinical stage and ki-67 and negatively correlated with p53 status.     

miR-200及其作用机制

miR-200是一簇与上皮间质转化(EMT)密切相关的微RNA(miRNA)家族,其家族成员包括miR-200a、miR-200b、miR-200c、miR-141及miR-429.miR-200是EMT的主要调节分子并可维持细胞的上皮表型,在EMT的发生和肿瘤的进展过程中发挥重要的作用.     

组蛋白脱乙酰基酶抑制剂在肿瘤治疗中的应用

组蛋白的乙酰化状态调控DNA转录从而影响基因的表达水平.组蛋白脱乙酰基酶(HDAC)可降低组蛋白乙酰化,引起DNA-组蛋白复合物压缩.这种压缩可以阻碍基因转录,抑制细胞分化.HDAC抑制剂可以解除DNA-组蛋白复合物压缩,从而促进肿瘤细胞生长停滞、分化及凋亡.在此过程中,HDAC抑制剂也影响非组蛋白的乙酰化状态和功能....     

实体肿瘤干细胞相关研究进展

肿瘤干细胞学说认为,肿瘤干细胞是肿瘤发生、生长、耐药以及复发、转移的根源.肿瘤不单是一种基因病,而且是一种干细胞病.越来越多的证据提示了多种实体瘤中肿瘤干细胞的存在.     

血清微小RNA(miR-129-3p、miR-767-3p和miR-877)在结直肠癌诊断中的价值

目的:探讨血清微小RNA (microRNA,mi RNA)在结直肠癌诊断中的价值.方法:通过miRNA表达谱芯片检测7例结直肠癌患者血清和10例健康志愿者血清中差异表达的miRNA.应用实时荧光定量PCR法在40例结直肠癌患者血清和18例健康志愿者血清中验证芯片结果,并分析血清特异性miRNA在结直肠癌诊断中的价值.结果:筛选获得10个在结直肠癌中特异性表达的血清miRNA,实时荧光定量PCR验证后获得一组结直肠癌特异性血清miRNA(miR-129-3p、miR-767-3p及miR-877*)生物标志物,这组生物标志物组合检测结直肠癌的灵敏度为77.78％、特异度为100％,并可产生最大受试者工作特征曲线(receiver operator characteristic curve,ROC)的曲线下面积(area under the curve,AUC)为0.914.结论:miR-129-3p、miR-767-3p和miR-877*生物标志物组合有望成为结直肠癌筛查和早期诊断的指标.     

血清中miR-29a和miR-92a在结直肠癌诊断和预后判断中的价值

目的探讨血清微小RNA（miR-29a和miR-92a）在结直肠癌（CRC）诊断和预后判断中的价值。方法选取无转移的结直肠癌患者50例和存在肝转移的患者48例,同时募集50名健康志愿者为对照组,按类似的年龄和性别相匹配的队列组合。应用实时荧光定量聚合酶链反应（PCR）法检测微小RNA（miR-29a和miR-92a）水平,判断该血清微小RNA在结直肠癌早期诊断和预后判断中的价值。结果结直肠癌患者血清中miR-29a和miR-92a水平均显著高于健康对照者（P〈0.01）;血清miR-29a和miR-92a分别进行结直肠癌诊断时的灵敏度为71.4%和75.3%,特异度为84.0%和88.3%;结直肠癌肝转移患者血清中miR-29a和miR-92a水平均显著高于未转移的CRC患者（P〈0.05）;miR-29a和miR-92a分别鉴别转移性与非转移性CRC患者的敏感性为79.4%和78.6%,特异性为85.3%和86.6%。结论 miR-29a和miR-92a可能是新的非侵入性指标用于结直肠癌患者的早期诊断,血清中miR-29a和miR-92a水平升高与结直肠癌患者预后有关,miR-29a和miR-92a有望成为结直肠癌筛查和早期诊断和预后判断的指标。     

微小RNA-203与肿瘤

微小RNA (miR)-203具有细胞干性抑制潜能,可通过抑制细胞干性相关转录因子的表达来调节细胞上皮样分化.研究表明miR-203在多种肿瘤组织中表达异常,包括膀胱癌、乳腺癌、结肠癌和胰腺癌等.miR-203通过调节细胞增殖、分化和凋亡在肿瘤的发生发展中发挥重要作用.     

Diagnostic and prognostic potential of serum miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429 in ovarian cancer patients

Background:

Owing to late diagnosis in advanced disease stages, prognosis of patients with epithelial ovarian cancer (EOC) is poor. The quantification of deregulated levels of microRNAs could facilitate earlier diagnosis and improve prognosis of EOC.

Methods:

Seven microRNAs (miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429) were quantified in the serum of 180 EOC patients and 66 healthy women by TaqMan PCR microRNA assays. Median follow-up time was 21 months. The effects of miR-7 and miR-429 on apoptosis, cell proliferation, migration and invasion were investigated in two (EOC) cell lines.

Results:

Serum levels of miR-25 (P=0.0001) and miR-93 (P=0.0001) were downregulated, whereas those of miR-7 (P=0.001) and miR-429 (P=0.0001) were upregulated in EOC patients compared with healthy women. The four microRNAs discriminated EOC patients from healthy women with a sensitivity of 93% and a specificity of 92%. The levels of miR-429 positively correlated with CA125 values (P=0.0001) and differed between FIGO I–II and III–IV stages (P=0.001). MiR-429 was an independent predictor of overall survival (P=0.011). Overexpressed miR-429 in SKOV3 cells led to suppression of cell migration (P=0.037) and invasion (P=0.011). Increased levels of miR-7 were associated with lymph node metastases (P=0.0001) and FIGO stages III–IV (P=0.0001). Overexpressed miR-7 in SKOV3 cells resulted in increased cell migration (P=0.001) and invasion (P=0.011). Additionally, the increased levels of miR-376a correlated with FIGO stages III–IV (P=0.02).

Conclusions:

Our data indicate the diagnostic potential of miR-7, miR-25, miR-93 and miR-429 in EOC and the prognostic potential of miR-429. This microRNA panel may be promising molecules to be targeted in the treatment of EOC.     

多重基因表达遗传分析系统及其在肿瘤研究中的应用

多重基因表达遗传分析系统是一种全新的基因表达谱定量分析平台.它采用荧光毛细电泳分离技术,巧妙地将通用引物与特异引物相结合,实现对多重PCR产物进行定量检测和分析.该技术简便快捷,产率高效,在肿瘤分型及标志物研究中具有广阔的应用前景.     

Circulating miR-148b and miR-133a as biomarkers for breast cancer detection

Circulating microRNAs have drawn a great deal of attention as promising novel biomarkers for breast cancer. However, to date, the results are mixed. Here, we performed a three-stage microRNA analysis using plasma samples from breast cancer patients and healthy controls, with efforts taken to address several pitfalls in detection techniques and study design observed in previous studies. In the discovery phase with 122 Caucasian study subjects, we identified 43 microRNAs differentially expressed between breast cancer cases and healthy controls. When those microRNAs were compared with published data from other studies, we identified three microRNAs, including miR-148b, miR-133a and miR-409-3p, whose plasma levels were significantly higher in breast cancer cases than healthy controls and were also significant in previous independent studies. In the validation phase with 50 breast cancer cases and 50 healthy controls, we validated the associations with breast cancer detection for miR-148b and miR-133a (P = 1.5×10⁻⁶ and 1.3×10⁻¹⁰, respectively). In the in-vitro study phase, we found that both miR-148b and miR-133a were secreted from breast cancer cell lines, showing their secretory potential and possible tumor origin. Thus, our data suggest that both miR-148b and miR-133a have potential use as biomarkers for breast cancer detection.