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。     

肝癌外周血循环微RNA的临床应用价值与展望

肝癌的早期诊断、有效的治疗和复发转移监测一直是困扰临床医师的难题。微RNA(miRNA)在肝癌细胞增殖、凋亡、代谢等过程中有重要作用, 并且其可以释放到血液、尿液和唾液等体液中。外周血中miRNA可作为肝癌诊断、疗效评估、复发转移监测和预后判断的生物标志物, 甚至可能成为肝癌的治疗靶标。文章就将外周血循环中的miRNA作为肝癌诊疗监测标志物的研究进展进行总结。     

外泌体源性miRNA在泌尿系统肿瘤诊疗中的研究进展

外泌体是存在于尿液、精液、血浆、血清、唾液等几乎所有体液的细胞外囊泡，含有丰富的miRNA，且外泌体中的miRNA可以反映来源细胞的miRNA表达情况。近年来，关于外泌体源性的miRNA作为泌尿系统肿瘤诊断标志物的研究发现，其在早期诊断、分级分期以及预后预测方面，尤其在早期诊断方面表现出了巨大的应用潜力，但在治疗效果评估方面的研究还比较有限。本文基于目前的研究进展，综述外泌体源性miRNA在泌尿系统肿瘤（膀胱癌、肾癌和前列腺癌）诊断中的应用。     

微小RNAs在乳腺癌中的应用价值

乳腺癌是目前女性最常见的恶性肿瘤,2012年全球共有170万乳腺癌新增病例,且乳腺癌的发病率和死亡率持续上升.肿瘤标志物在乳腺癌的早期诊断、个体化治疗、预后及疗效预测等方面发挥重要作用.目前常见的肿瘤标志物包括蛋白酶类、肿瘤特异性抗原、代谢产物等.然而,这些标志物特异性并不高,特别是在肿瘤早期筛查、良恶性肿瘤的区分和低度恶性肿瘤的诊断方面特异性较低.微小RNA（microRNA,miRNA）是一类调控基因表达的非编码小分子RNA,参与多种生物学信号通路的调节,组织或循环中miRNA的异常表达与乳腺癌密切相关.循环miRNA作为非侵袭性、实时监测的新型肿瘤标志物,在乳腺癌领域得到了广泛研究,可以作为分析肿瘤转移、预后判断、疗效评价和个体化治疗的有利依据.本文介绍miRNA与乳腺癌的相关性,并针对循环miRNA在乳腺癌的诊断、预后以及疗效评价方面的应用价值作一综述.     

肺癌诊治和预后判断分子标志物miRNA

肺癌是目前全世界发病率第一、死亡率最高的肿瘤。肺癌的早期诊断和有效治疗是提高患者生存率的关键。miRNA是一类内源性、高度保守的非编码小分子RNA,在肺癌的发生、发展中起着重要作用。近年来,肺癌诊断、治疗和预后判断分子标志物miRNA的研究进展迅速,本文就miRNA作为肺癌早期诊断、预后判断和疗效预测分子标志物的研究进展,以及目前存在的问题做一综述。      

新型肿瘤分子标志物循环微小RNA的研究进展

肿瘤作为威胁人类健康的最主要疾病之一,早期诊断、个体化治疗方案的选择及复发的判断对于预后有重要意义.微小RNA（miRNA）是一类具有调节作用的小片段RNA分子,近几年逐渐成为研究热点.miRNA分子在体液及循环系统中稳定存在,而且某些miRNA在肿瘤患者中特异性表达,对肿瘤的诊断及预后具有指导意义.文章综述有关循环miRNA的研究报道,探讨循环miRNA作为新型肿瘤分子标志物的意义及其局限性.     

液态活检miR-509-5p/miR-124比值诊断膀胱癌的临床应用

背景与目的:液态活检是一种从血液、尿液等非实体生物组织中取样分析,主要用于恶性肿瘤诊断、监测及判断预后的方法.该研究通过优化尿液miRNA的提取方法,建立标准化的液态活检手段,筛选并验证膀胱癌患者尿液miRNA标志物以阐明其临床应用价值.方法:收集2014年1月—2015年9月膀胱癌患者及健康对照者的尿液,应用miRNA表达谱芯片进行筛选,在78例膀胱癌患者及23例健康对照者的晨尿中进行实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)验证,分析液态活检的miRNA标志物与膀胱癌临床病理的关系及其诊断价值.结果:通过对6例膀胱癌及6例健康对照者的尿液miRNA表达谱进行分析,筛选出了10个miRNA有差异表达,结合既往文献报道的膀胱癌尿液miRNA标志物,我们挑选了20个miRNA进行RTFQ-PCR验证,发现miR-509-5p/miR-124比值在膀胱癌患者尿液中表达水平较健康对照者高,差异有统计学意义(P<0.0001).尿液miR-509-5p/miR-124比值随着患者肿瘤分期和肿瘤分级的上升而升高(P=0.003).当界值定在0.41时,miR-509-5p/miR-124比值对膀胱癌的诊断灵敏度为73.1%,特异度为82.6%,曲线下面积(area under the curve,AUC)达到0.864,比尿液脱落细胞学的诊断价值高(P=0.0002).结论:该研究优化了尿液miRNA的提取方法,建立了标准化的液态活检尿液miRNA标志物的检测手段,发现miR-509-5p/miR-124比值可能是膀胱癌理想的诊断标志物.     

microRNA在胃癌中的生物学作用

microRNA（miRNA）是一类含量丰富且高度保守的非编码小RNA分子,调控细胞分裂、分化、调亡等重要的生物学过程,并且在很多疾病中表达失调。miRNA在多种肿瘤的发生、发展中发挥重要作用。目前,对miRNA的研究正逐步从肿瘤分子研究走向临床应用领域,作为生物标志物用于癌症的诊断以及作为靶分子用于治疗已逐渐得到确认。本文对miRNA在胃癌中作为一个潜在的生物标志物用于诊断、预后、药物反应以及易感性的预测等方面的潜能进行综述。      

微小 RNA：胆管癌中新的调节分子与生物标志物

微小 RNA（miRNA）与胆管癌（CCA）的发生发展、浸润、转移和预后密切相关。CCA 细胞中异常表达的 miRNA 在调控细胞遗传变异、细胞周期、浸润转移能力及其凋亡过程中起重要作用,有望作为 CCA 早期诊断、预后判断的生物学标志物及治疗靶点。     

miRNA在卵巢癌早期诊断和预后中作用的研究进展

[摘要] 卵巢癌是女性生殖器官常见的恶性妇科肿瘤之一。由于缺乏有效的生物标志物用于诊断和个性化治疗,超过70％的卵巢癌患者诊断时已是晚期,并且5 年生存率低于30％。因此,迫切需要新的诊断和预后标志物来推进和启动更个性化的治疗,最终提高患者的存活率。miRNA是一类小的非编码RNA,主要通过转录后抑制负调节基因表达。近年来,一些研究表明,miRNA在卵巢癌组织中表达失调,有可能作为卵巢癌的诊断和预后生物标志物。另外,最近的研究显示,miRNA还可以作为化疗敏感性的预测因子和治疗靶点。本文主要从miRNA在卵巢癌组织中的差异表达、miRNA与卵巢癌的诊断和miRNA与卵巢癌的预后3 个方面进行阐述,为推进和启动卵巢癌患者的诊断和个性化治疗提供借鉴。     

MicroRNAs as diagnostic and prognostic biomarkers in colorectal cancer

MicroRNAs (miRNAs) are key regulators involved in various tumors. They regulate cell cycle, apoptosis and cancer stemness, metastasis and chemoresistance by controlling their target gene expressions. Here, we mainly discuss the potential uses of miRNAs in colorectal cancer (CRC) diagnosis. We also shed light on the important corresponding miRNA targets and on the major regulators of miRNAs. Furthermore, we discuss miRNA activity in assessing the prognosis and recurrence of CRC as well as in modulating responsiveness to chemotherapy. Based on the various pro-oncogenic/anti-oncogenic roles of miRNAs, the advantages of a therapeutic strategy based on the delivery of miRNA mimics are also mentioned. Together, miRNA seems to be an excellent tool for effectively monitoring and targeting CRC.     

MicroRNAs as potential biomarkers in human solid tumors

MicroRNAs (miRNAs) regulate the expression of approximately 30% of protein-coding genes. Functions of miRNAs are essential to maintain a steady state of cellular machinery. Dysregulations of miRNAs play pivotal roles in the initiation and progression of malignancies. Abnormal miRNA expressions have been found in a variety of human solid tumors. Furthermore, extracellular miRNAs could circulate in body fluids, and hence show great promise for refining diagnosis and prognosis of cancer. Here we review the progress of analysis of microRNAs as a potential approach for diagnosis and prognosis of solid cancer. We will also discuss obstacles in developing miRNAs as circulating biomarkers.     

循环microRNA在胃癌临床诊断及预后中的研究进展

microRNAs（miRNAs）是一类长约22个核苷酸的内源性非编码RNA分子,通过与靶基因mRNA 3'-非编码区相互作用引起靶基因mRNA降解或翻译抑制,在转录后水平发挥着重要的调控功能。有关miRNA在癌症中的功能已经进行了广泛研究,最近发现外周血等体液中存在miRNA,并且多种癌症患者的外周血miRNA表达谱发生特异性改变。越来越多证据表明循环miRNA可作为一种新颖的分子标志物应用于癌症诊断和预后评估。本文针对循环miRNA在胃癌诊断、评估和预后等方面的研究进展进行综述。     

The Research Progress of the Interactions between miRNA and Wnt/beta-catenin Signaling Pathway in Breast Cancer of Human and Mice

MicroRNA expression is a research focus in studies of tumors. This article concentrates attention on potentiallinks between tumors caused by mouse mammary tumor virus (MMTV) and human breast cancer, in orderto provide theoretical basis for using mouse model to search for miRNA effects mediated by Wnt/beta-cateninsignaling in human breast cancer. By analyzing interactions between miRNAs and the Wnt/beta-catenin signalingpathway in breast cancer, we hope to casts light on more biological functions of miRNAs in the process of tumorformation and growth and to explore their potential value in cancer diagnosis, prognosis and treatment. Ourendeavor aimed at providing theoretical basis for finding safer, more effective methods for treatment of humanbreast cancer at the miRNA molecular level.     

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.     

MicroRNA expression profiling in prostate cancer

MicroRNAs (miRNA) are small, endogenously expressed noncoding RNAs that negatively regulate expression of protein-coding genes at the translational level. Accumulating evidence, such as aberrant expression of miRNAs, suggests that they are involved in the development of cancer. They have been identified in various tumor types, showing that different sets of miRNAs are usually deregulated in different cancers. To identify the miRNA signature specific for prostate cancer, miRNA expression profiling of 6 prostate cancer cell lines, 9 prostate cancer xenografts samples, 4 benign prostatic hyperplasia (BPH), and 9 prostate carcinoma samples was carried out by using an oligonucleotide array hybridization method. Differential expression of 51 individual miRNAs between benign tumors and carcinoma tumors was detected, 37 of them showing down-regulation and 14 up-regulation in carcinoma samples, thus identifying those miRNAs that could be significant in prostate cancer development and/or growth. There was a significant trend (P=0.029) between the expression of miRNAs and miRNA locus copy number determined by array comparative genomic hybridization, indicating that genetic aberrations may target miRNAs. Hierarchical clustering of the tumor samples by their miRNA expression accurately separated the carcinomas from the BPH samples and also further classified the carcinoma tumors according to their androgen dependence (hormone naive versus hormone refractory), indicating the potential of miRNAs as a novel diagnostic and prognostic tool for prostate cancer.     

The miRNA-200 family and miRNA-9 exhibit differential expression in primary versus corresponding metastatic tissue in breast cancer

Metastases are the major cause of cancer-related deaths, but the mechanisms of the metastatic process remain poorly understood. In recent years, the involvement of microRNAs (miRNAs) in cancer has become apparent, and the objective of this study was to identify miRNAs associated with breast cancer progression. Global miRNA expression profiling was performed on 47 tumor samples from 14 patients with paired samples from primary breast tumors and corresponding lymph node and distant metastases using LNA-enhanced miRNA microarrays. The identified miRNA expression alterations were validated by real-time PCR, and tissue distribution of the miRNAs was visualized by in situ hybridization. The patients, in which the miRNA profile of the primary tumor and corresponding distant metastasis clustered in the unsupervised cluster analysis, showed significantly shorter intervals between the diagnosis of the primary tumor and distant metastasis (median 1.6 years) compared to those that did not cluster (median 11.3 years) (p<0.003). Fifteen miRNAs were identified that were significantly differentially expressed between primary tumors and corresponding distant metastases, including miR-9, miR-219-5p and four of the five members of the miR-200 family involved in epithelial-mesenchymal transition. Tumor expression of miR-9 and miR-200b were confirmed using in situ hybridization, which also verified higher expression of these miRNAs in the distant metastases versus corresponding primary tumors. Our results demonstrate alterations in miRNA expression at different stages of disease progression in breast cancer, and suggest a direct involvement of the miR-200 family and miR-9 in the metastatic process.