结直肠癌miRNA相关基因单核苷酸多态性与预后相关性研究现状

目的:总结microRNA(miRNA)相关基因单核苷酸多态性(single nucleotide polymorphism,SNP)与结直肠癌患者预后的相关性研究,探讨miRNA相关基因SNPs在结直肠癌患者中的预后价值。方法:应用Medline及PubMed全文数据库检索系统,以"miRNA、单核苷酸多态性、癌症和预后"等为关键词,检索2008-07-2013-10的相关文献。纳入标准:1)miRNA相关基因SNP在癌症中的研究现状;2)miRNA相关基因SNP与结直肠癌患者预后的相关性研究。符合要求并纳入分析的文献39篇。结果:miRNAs是一类非编码小RNAs,可以与靶基因mRNA分子3′非翻译区域特异性结合来负调控蛋白表达。miRNA的突变、缺失或表达水平异常与肿瘤的发生发展密切相关。miRNAs表达水平的异常可作为结直肠癌预后相关的标志。编码miRNA的基因及相关的靶基因结合位点中也存在SNP,其可能通过miRNA转录、miRNA前体形成以及miRNA与mRNA的结合这3种不同的机制影响miRNA的调控,从而来影响结直肠癌患者的预后。miRNA相关基因SNPs(pre-miR-423的rs6505162、pre-miR-608的rs4919510、mir608的rs4919510、mir219-1的rs213210以及let-7f-2的rs17276588),在结直肠癌患者中的预后价值可能与肿瘤分期及治疗有关。结论:miRNA相关基因SNPs可作为预测结直肠癌患者预后的替代标志。     

MicroRNA与结直肠癌化疗关系的研究进展

化疗是结直肠癌的重要治疗手段,然而肿瘤药物治疗的疗效存在个体差异,耐药是化疗过程中面临的主要问题。microRNA(miRNA)是一类小分子非编码RNA,能够在转录后水平调控蛋白合成。研究显示,miRNA通过不同的机制引起肿瘤细胞的抗药性,与结直肠癌化疗的反应性相关。     

MicroRNA及其基因甲基化在结直肠癌的临床应用研究进展

微小RNA（microRNA,miRNA）是一类长18-25个核苷酸的非编码单链小分子RNA。近些年来,越来越多的研究提示miRNA表达异常参与肿瘤干细胞的自我更新、多能性维持、分化和分裂增殖等过程的调控。在消化系统肿瘤中尤其是在结直肠癌方面miRNA相关的研究较为深入。多项研究结果显示,miRNA及其基因甲基化在结直肠癌的早期检测及诊断、化疗疗效预测及预后预测方面都有着重要的意义。     

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。     

microRNA在结直肠癌中的研究进展

microRNA(miRNA)是一类长21-25nt核苷酸的内源性非编码调控RNA,通过与靶细胞mRNA的3’UTR完全互补导致mRNA降解,或不完全互补结合阻断mRNA翻译,参与细胞发育、增殖、分化和凋亡。miRNA具有癌基因和抑癌基因的作用,若干miRNA直接或间接参与结直肠癌的发生和发展,miRNA表达谱与结直肠癌的诊断、分期、进展和预后密切相关。     

结直肠癌中miRNA基因及其靶基因多态性位点的研究进展

结直肠癌是最常见的消化系统肿瘤之一。近年来的研究表明,miRNA在结直肠癌的发病过程起着重要的作用。由于单核苷酸多态性（SNPs）的存在,miRNA的结构和功能可能发生变化,从而影响结直肠癌的发病率。目前国内外对miRNA及其靶基因多态性与结直肠癌的关系研究不多。在本文中,我们将对结直肠癌中miRNA表达谱的改变、miRNA基因及其靶基因多态性与结直肠癌的关系及miRNA基因多态性对于结直肠癌的诊断、预后判断、预测疗效的应用前景等内容进行综述。     

microRNA在结直肠癌中的研究进展

microRNA（miRNA）是一类长21-25nt核苷酸的内源性非编码调控RNA,通过与靶细胞mRNA的3＇UTR完全互补导致mRNA降解,或不完全互补结合阻断mRNA翻译,参与细胞发育、增殖、分化和凋亡。miRNA具有癌基因和抑癌基因的作用,若干miRNA直接或间接参与结直肠癌的发生和发展,miRNA表达谱与结直肠癌的诊断、分期、进展和预后密切相关。     

血清miRNA作为结直肠癌患者诊断标志物的价值研究

[目的]探讨特征性血液miRNA作为结直肠癌诊断标志物的可行性.[方法]用miRNA的定量PCR芯片,从结直肠癌患者和健康对照者血清中筛选出候选的特征性miR-NA.再以线虫cel-39作为外参,采用相对定量法分析36例结直肠癌患者及25名健康对照者血清中候选miRNA表达情况.[结果]9条miRNA呈特征性表达,其中5条miRNA明显上调,4条明显下调;9条特征性表达的miRNA均得以验证.将9条特征性血清miRNA进行聚类分析,可见其能够清晰地将结直肠癌患者与健康对照者分为两类.采用ROC曲线分析发现被检测结直肠癌样本的曲线下面积(AUC)达0.934 (95％CI:0.877～0.992)(P＜0.001).[结论]miR-21等9条miRNA组合检测可作为结直肠癌诊断的生物标志物.     

血浆hsa-miR-150和hsa-miR-375在结直肠癌中的表达及意义

目的:筛选结直肠癌患者血浆微小RNA(microRNA,miRNA),并寻找与临床特征相关的miRNA。方法:通过TaqMan Human Micro RNA Array检测7例结直肠癌患者和6例健康体检者血浆中差异表达的miRNA,应用实时荧光定量PCR在29例结直肠癌患者和20例健康体检者中对TaqMan Human Micro RNA Array检测结果进行验证,分析血浆差异表达的miRNA与结直肠癌患者临床特征之间的关系。结果:在变化倍数>1.0,P<0.05的条件下初步筛选得到16个结直肠癌患者血浆差异表达miRNA,实时荧光定量PCR验证得到hsa-miR-125b、hsa-miR-375、hsa-miR-150和hsa-miR-206与TaqMan Human Micro RNA Array检测结果一致,并且在结直肠癌患者和健康体检者血浆中的表达差异有统计学意义(P<0.05)。同时发现,血浆hsa-miR-150和hsa-miR-375表达水平与肿瘤的浸润深度或脉管瘤栓有关。结论:血浆hsa-miR-150和hsa-miR-375有望成为一种非侵入性的指导结直肠肿瘤分期和进行预后评估的分子标志物。     

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.     

结直肠癌中microRNA标志物临床诊断价值的研究进展

结直肠癌是最常见的消化道恶性肿瘤,其发生、发展及诊疗、预后已成为当前临床研究关注 的热点。microRNAs (miRNAs) 是一类内源性的、19~25个碱基长度的小分子非编码RNA,在人体生命 活动中具有广泛的调节功能。目前发现,部分miRNAs异常表达与结直肠癌的发生、发展密切相关,提 示miRNAs可作为结直肠癌临床早期诊断及预后评估的特异性新型生物标志物。文章综述了miRNAs作 为结直肠癌临床早期诊断、预后和治疗结果评估生物标志物的研究进展,揭示结直肠癌miRNAs参与的 基因表达调控机制, 展望miRNAs作为结直肠癌新型诊断分子标志物及治疗靶点的广阔临床应用前景。     

大肠癌相关miRNA研究进展

大肠癌是消化系统的常见恶性肿瘤,其发病率近年来在我国不断上升。大量研究证实,miRNA作为一类保守非编码RNA,可能与大肠癌的发生、侵袭以及转移等关系密切。大肠癌中miRNA表达谱差异较大,目前研究比较多的 miRNAs如miRNA-145、miRNA-489、miRNA-34a等均有抑制肿瘤细胞生长增殖的作用,它们在癌细胞中表达下降,通过不同的信号途径实现对靶基因表达的调控参与大肠癌的发生。提示对于大肠癌相关 miRNA作用机制的研究将可能为大肠癌诊断治疗提供新策略和思路。     

外泌体作为结直肠癌诊断标志物的研究进展

外泌体是一种由细胞分泌至胞外的直径为30~150 nm的纳米囊泡，广泛分布于人体血液、尿液、唾液、汗液、乳汁和脑脊液等多种体液中。结直肠癌是常见的消化道恶性肿瘤，其发病率在全球范围内位居第三，严重威胁着人类健康。结直肠癌来源的外泌体中含有一些肿瘤特异性蛋白、微小RNAs（microRNAs，miRNAs）和长链非编码 RNAs（long non-coding RNAs，lncRNAs）等，与结直肠癌的发生和发展具有相关性，因此有望作为结直肠癌诊断的生物标志物。本文主要对外泌体在结直肠癌诊断中的应用前景作一综述。     

miR-124, miR-137 and miR-340 regulate colorectal cancer growth via inhibition of the Warburg effect

Colorectal cancer represents one of the most challenging diseases. Increasing evidence indicates that aberrant expression of microRNAs (miRNAs) is related to pathogenesis of colorectal cancer. Cancer cells reprogram metabolic pathways to sustain higher proliferation rates. Whether mechanisms underlying the role of miRNA in colorectal cancer are involved in metabolic reprogramming and the mechanisms through which miRNAs alter cancer metabolism are as yet unknown. Herein, we show that miR-124, miR-137 and miR-340 are associated with poor prognosis of colorectal cancer. Expression of these miRNAs inhibits the growth of colorectal cancer cells. PKM (pyruvate kinase isozyme) alternative splicing proteins (PTB1/hnRNAPA1/hnRNAPA2), which control the inclusion of exon 9 (PKM1) or exon 10 (PKM2), are targeted by miR-124, miR-137 and miR-340. Consequently, miR-124, miR-137 and miR-340 switch PKM gene expression from PKM2 to PKM1. High ratios of PKM1/PKM2 inhibit the glycolysis rate, but elevate the glucose flux into oxidative phosphorylation. These results demonstrate that miRNAs (miR-124, miR-137 and miR-340) impair colorectal cancer growth by counteracting the Warburg effect due to regulating alternative splicing of the PKM gene.     

MicroRNAs in colorectal cancer: translation of molecular biology into clinical application

MicroRNAs (miRNAs) are small non-coding RNAs 18-25 nucleotides in length that downregulate gene expression during various crucial cell processes such as apoptosis, differentiation and development. Changes in the expression profiles of miRNAs have been observed in a variety of human tumors, including colorectal cancer (CRC). Functional studies indicate that miRNAs act as tumor suppressors and oncogenes. These findings significantly extend Vogelstein's model of CRC pathogenesis and have shown great potential for miRNAs as a novel class of therapeutic targets. Several investigations have also described the ability of miRNA expression profiles to predict prognosis and response to selected treatments in CRC patients, and support diagnosis of CRC among cancer of unknown primary site. miRNAs' occurrence has been repeatedly observed also in serum and plasma, and miRNAs as novel minimally invasive biomarkers have indicated reasonable sensitivity for CRC detection and compare favorably with the fecal occult blood test. In this review, we summarize the knowledge regarding miRNAs' functioning in CRC while emphasizing their significance in pathogenetic signaling pathways and their potential to serve as disease biomarkers and novel therapeutic targets.     

Identification of aberrantly expressed miRNAs in rectal cancer

Disturbance of miRNA expression may play a key role in the initiation and progression of colorectal cancer (CRC). CRC should be viewed as a heterogeneous disease, but previous studies have only screened dysregulated miRNAs in CRC from a panel of 96, 145, 287 and 455 miRNAs, respectively. It is necessary to identify new aberrantly expressed miRNAs in rectal cancer. In this study tissue samples were derived from patients undergoing a surgical procedure to remove a portion of cancers. The expression profile of 904 miRNAs was analyzed using a miRCURY? LNA Array from 6-paired rectal cancers and normal tissues. The expression levels of 4 miRNAs were compared by real-time PCR between colon and rectal cancer, and also the expression levels of metastatic miRNAs in different stages of rectal cancer were analyzed. We found that 67 miRNA precursors are upregulated in rectal cancer (p<0.05) and 21 of those have never been reported in colorectal cancer (CRC); 39 miRNA precursors are downregulated (p<0.05) and 24 novel dysregulated miRNAs were identified in rectal cancer. miR-31, miR-126 and miR-143 are differentially expressed between colon cancer and rectal cancer. Here, we report an miRNA profile of rectal cancer, and we identified differential expression patterns of miRNAs between rectal and colon cancers. This novel information may suggest the potential roles of these miRNAs in the diagnosis of rectal cancer.     

Down-regulation of miR-126 expression in colorectal cancer and its clinical significance

MicroRNAs (miRNAs) are non-coding RNAs that regulate the expression of target mRNAs. Altered expression of specific miRNAs in several tumor types has been reported. However, the expression levels of miR-126 in colorectal cancers are unclear. In this study, we compared the expression of miR-126 between colorectal cancer tissues and non-tumor tissues. The expression levels of miR-126 in colorectal cancer tissues were significantly lower than those in non-tumor tissues, and miR-126 overexpression inhibited the growth of colorectal cancer cells. This new information may help to clarify the molecular mechanisms involved in colorectal carcinogenesis and to indicate that miR-126 may be a novel suppressive microRNA and help to differentiate between malignant and normal colorectal tissue.