MicroRNA与乳腺癌关系的研究进展

MicroRNAs（miRNAs）是一类广泛存在于真核细胞中的长约21-22 nt的单链、非编码小RNA,具有转录后基因调控的功能,参与调控胚胎发育、细胞生长和凋亡、细胞分化、细胞能量代谢等多种生理过程以及糖尿病、心血管疾病、神经系统疾病、肿瘤等多种病理过程。近些年来研究发现,miRNAs与乳腺癌之间的关系十分密切。本文综述与乳腺癌发生、发展密切相关的miRNAs。     

微小核糖核酸在乳腺癌中的研究进展

微小核糖核酸(miRNAs)是一类具有调控功能的小分子非编码核糖核酸,与人类众多疾病的发生有关。miRNAs稳定性好,可反复取样检测,被认为是最具潜力的肿瘤标志物之一。研究证实了miRNAs对乳腺癌发生发展、侵袭转移、诊断治疗及预后检测的作用。本文就近年来该方面的研究进展进行综述。     

β-elemene通过调节耐药特异性miRNA逆转乳腺癌细胞耐药性的机制研究

目的:探讨β-榄香烯逆转乳腺癌细胞耐药性的机制,明确其抗肿瘤作用。方法:通过向MCF-7细胞株培养基内逐渐增加临床上最常用于乳腺癌化学治疗的药物多西紫杉醇(Doc)或阿霉素(Adr),逐渐提高培养基中药物浓度的方法成功地构建出亲本细胞株MCF-7中耐药亚型,选择乳腺癌阿霉素耐药细胞(MCF-7/Adr)和乳腺癌多西紫杉醇(MCF-7/Doc)耐药细胞株,采用MTT-cytotoxic、miRNA微阵列、实时定量PCR、双荧光素酶活性测定等方法,研究β-elemene对乳腺癌耐药细胞生存率、耐药特异性miRNA29a、miRNA452、miRNA34a及miRNA222表达的影响。结果:β-elemene明显降低耐药乳腺癌细胞株细胞生存率和增殖率,β-elemene显著调节MCF-7/Adr和MCF-7/Doc细胞内miRNAs的表达水平,其中6个miRNAs上调,12个miRNAs下调显著。结论:β-elemene是一种从植物中提取的天然抗肿瘤中药成分,可以逆转乳腺癌细胞的耐药性。证实了中药β-elemene可以通过调控耐药相关miRNA表达的机制抗乳腺癌耐药细胞的耐药性。     

循环miRNAs检测对乳腺癌诊断价值的meta分析

目的：评价循环miRNAs对乳腺癌的诊断价值。方法检索 PubMed,Embase和 Cochrane外文数据库以及中国知网、维普、万方等中文数据库2014年6月之前发表的相关文献,12篇参考文献纳入研究,采用 Meta-Disc1.4软件统计,随机效应模型计算合并敏感度、特异度、阳/阴性似然比和诊断比值比,以sROC曲线法分析miRNAs总体诊断性能。采用stata12.0软件分析现有的参考文献是否存在发表偏倚。结果循环 miRNAs诊断乳腺癌的合并灵敏度是80％（95％CI 0.77～0.82）,合并特异度是78％（95％CI 0.75～0.81）;合并阳性似然比是4.09（95％CI 2.80～5.99）,合并阴性似然比是0.22（95％CI 0.15～0.31）;合并诊断比值比是20.64（95％CI 10.24～41.62）;sROC曲线下面积（AUC）为0.89,Q值为0.82。已有的研究存在发表偏倚。结论循环miRNAs可作为一项潜在的生物标记物用于乳腺癌的诊断。     

MicroRNAs与心力衰竭的诊断和治疗

MicroRNAs（miRNAs）是一类内源性的具有调控功能的非编码RNA ,其大小长约20～25个核苷酸。成熟的miRNAs是由较长的初级转录物经过一系列核酸酶的剪切加工而产生的,通过碱基互补配对的方式识别mRNA ,并根据互补程度的不同指导降解靶mRNA或者阻遏mRNA的翻译。研究表明, miRNAs参与各种各样的调节途径,包括发育、病毒防御、造血过程、器官形成、细胞增殖和凋亡、脂肪代谢等。目前,在人类基因组内超过1500 miRNAs 已经被鉴定（www ．mirbase ． org）,并且随着生物信息学及高能量测序技术的进步,相信有更多的miRNAs被发现。研究已经发现众多特异的miRNAs参与了心脏发育、病理改变,而在心力衰竭的病理生理过程中也发现了一系列的miRNAs参与其中。本文现针对miRNAs与心力衰竭的诊断和治疗展开综述。     

microRNAs的定量分析技术及其应用

本文评述了微小RNA(microRNAs,miRNAs)定量分析技术及其应用,重点介绍了miRNAs定量检测的各种方法、各自特点及其在检测过程中可能遇到的问题,为miRNAs的定量分析和研究提供参考。     

MicroRNAs作为结直肠癌潜在标记物的研究进展

微小RNA(miRNAs)是一种非编码的内源性RNA分子,miRNAs 的异常表达与疾病,尤其与恶性肿瘤的发生、发展存在密切的关系。研究证明,miRNAs可以作为结直肠癌(colorectal cancer,CRC)早期诊断、治疗、预后的新的分子生物学标志物,同时,miRNAs可作为体内CRC治疗的靶点。该文旨在对与CRC相关的miRNAs的表达、功能、作用机制、靶基因等及其在临床应用前景等方面作一综述。     

microRNAs与心肌梗死

microRNAs（miRNAs）是一类内源性的非编码单链小分子RNA,约22个核苷酸。miRNAs通过调控其靶基因的表达,参与细胞发育、增殖、分化、凋亡等一系列重要的生理学途径。近些年的研究发现,miRNAs在心肌梗死的发生、发展过程中起着关键的作用。现就miRNAs在心肌梗死发生、发展过程中的作用机制进行阐述。     

MicroRNAs与动脉粥样硬化

哺乳动物细胞内microRNAs (miRNAs)的发现使对疾病研究的重点转向转录后调节机制方面。在心血管系统中发现多种miRNAs与动脉粥样硬化病的发生发展密切相关。本文从动脉粥样硬化各大学说板块的角度,综述miRNAs在动脉粥样硬化发病机制中的作用和进展。     

microRNAs与心血管疾病

摘要： 微小核糖核酸（microRNAs, miRNAs）是一类内源性非编码单链小分子RNAs,主要在基因转录后水平调控靶基因的表达。研究发现,miRNAs参与调控心血管疾病（CVD）的多种病理、生理过程,包括心肌肥大、心律失常以及血管生成等。循环miRNAs稳定性高,可望作为CVD诊断的新型标志物和治疗靶点。本文就miRNAs与CVD的最新研究进展进行综述。     

基于TCGA数据库筛选微小RNA（miRNA）用于原发性乳腺癌早期诊断的生物信息学分析

目的　基于肿瘤基因图谱（the cancer genome atlas,TCGA）数据库筛选微小RNA（miRNA）用于原发性乳腺癌的早期诊断。方法　从TCGA上下载原发性乳腺癌miRNA表达数据,将癌症组与正常组比较获得差异表达miRNA。用miRwalk2.0软件分析差异miRNA的靶基因。在c-Bioportal数据库中筛选出原发性乳腺癌突变发生率大于5%的突变基因。分析差异miRNA作用的靶基因与乳腺癌高频突变基因之间的关系,得到备选miRNA,将备选miRNA与乳腺癌前20 名差异表达的miRNA求交集,得到目标miRNA,将目标miRNA做受试者工作曲线（ROC曲线）分析。结果　TCGA数据包含原发性乳腺癌组织1 075例,正常对照乳腺组织95例,共有1 870条miRNA的表达数据。共得到差异表达显著miRNA 129个（P＜0.05）,其中乳腺癌组织中表达升高至3倍以上的miRNA 90个,下调至1/3的miRNA 39个,预测到相对应18 413个靶基因,筛选出原发性乳腺癌突变基因12个。18 413个靶基因中包含12个高频基因,此12个基因是差异miRNA的靶基因同时也是高频基因,故将此12个基因对应的63个miRNA作为备选miRNA。将备选miRNA与乳腺癌前20 名差异表达的miRNA求交集得到目标miRNA 6个:hsa-mir-4732,hsa-miR-486,hsa-miR-592,hsa-miR-449b,hsa-miR-187和hsa-miR-196a,将这 6个miRNA构建ROC曲线（P＜0.05）,预测其作为肿瘤标志物的诊断能力。结论　基于TCGA数据库的生物信息学方法可简便而可靠地筛选目标miRNA进行后续研究,有较高的参考价值。     

Tumor suppressor microRNAs: Targeted molecules and signaling pathways in breast cancer

Breast cancer is the most common type of cancer in women whose prevalence is increasing every year. Common strategies for diagnosis, prognosis and specific treatment of breast cancer need improvements to increase patients’ survival. For this reason, there is growing number of efforts world-wide with molecular approaches. With the advent of microRNAs (miRNAs), they have been interested for almost all aspects of tumorgenesis and correlation of breast cancer and microRNAs was discovered for the first time in 2005. MiRNAs form a group of small noncoding RNAs which participate in regulation of gene expression and subsequently several biological processes and pathogenesis of various diseases. As other cancers, miRNAs involved in breast cancer are classified in two groups: the first group is tumor inducing miRNAs (also called oncomirs) that can induce tumor initiation and progression, and their expression is increased in cancerous cells. The second group is tumor suppressor miRNAs. In normal situation, tumor suppressor miRNAs prevent beginning and progression of breast cancer through suppressing the expression of various oncogenes. In this review we will give a general overview about miRNAs and breast cancer, and in the following, more discussion about tumor suppressor miRNAs, with focus on the best known of them and their targeted oncogenes and signaling pathways. Finally, we will point to application of this group of miRNAs in diagnosis, prognosis and treatment of patients.     

血清微小RNA作为早期乳癌诊断标志物的价值

目的探讨血清5种微小RNA（miRNA）在乳癌早期诊断中作为生物标记物的价值。方法根据生物信息学数据库miRWalk的预测,选定5种与乳癌相关的miRNA（包括miR-31、miR-107、miR-155、miR-200c及miR-205）。采用实时荧光定量PCR检测5种miRNA在42例健康女性、66例乳癌病人中的相对表达量,根据受试者工作特征曲线（ROC曲线）下面积分析诊断乳癌的特异度和灵敏度。结果血清中miR-31、miR-107和miR-200c联合检测诊断乳癌的灵敏度为78.6%,特异度为88.7%。结论血清中miR-31、miR-107和miR-200c的组合有可能成为乳癌早期诊断的新指标。     

microRNAs: a new class of breast cancer biomarkers

MicroRNAs (miRNAs) are regulatory molecules known to be aberrantly expressed in cancer and contribute to numerous aspects of tumor biology including the initiation, growth and spread of the tumor. With such diverse roles, it is becoming apparent that some may also provide valuable information which may be of use in a clinical setting, demonstrating the potential to act as both screening tools for the stratification of high-risk patients, while informing the treatment decision-making process. There is mounting evidence to suggest that some miRNAs may even provide assistance in the diagnosis of patients with breast cancer. In addition, miRNAs may themselves be considered therapeutic targets, with inhibition or reintroduction of a particular miRNA capable of inducing a response in vivo. This review focuses on miRNAs that have prognostic, diagnostic or predictive potential in breast cancer as well as the possible challenges in the translation of such observations to the clinic.     

Potential diagnostic role of circulating MiRNAs in breast cancer: Implications on clinicopathological characters

BackgroundCirculating miRNAs are stable in body fluids and resembles their levels in cancer tissue/cells. They have been expressed in many cancers among them is breast cancer. Authors aimed to investigate the expression levels of three circulating oncomiRNAs (miRNA-21, miRNA-222 and miRNA-373) in serum samples as a minimally non-invasive method for early detection of breast cancer, and study their relation with clinicopathological characters.MethodsMiRNAs expression levels were determined using quantitative real-time polymerase chain reaction (qPCR) in serum samples from three groups: primary breast cancer patients (n = 137), benign breast lesion patients (n = 60), and healthy individuals as control group (n = 38). Statistical analyses were carried out using SPSS.ResultsSignificant differences were observed between the expression levels of the studied miRNAs in the investigated groups, as their median levels were increased in breast cancer patients followed by benign group patients then the healthy individuals. MiRNA-373 reported the highest diagnostic efficacy as compared to miRNA-21 and miRNA-222 with high area under the curve (AUC equals 0.987). The relation between tested miRNAs and clinicopathological factors revealed significant difference with clinical stages and histological grades. Level of miRNA-21 and miRNA-373 were statistically significantly higher in invasive duct carcinoma (IDC) as compared to non-IDC. Similarly, their levels were increased in lymph node metastasis (P < 0.01). MiRNA-222 and miRNA-373 were significantly increased in positive PgR and positive Her-2/neu status, respectively.ConclusionAssessment of miRNAs in serum samples can be applied as minimally non-invasive markers for early detection of breast cancer, and as discriminator between different clinicopathological characters.     

The potential of miRNAs for diagnosis,treatment and monitoring of breast cancer

Abstract

Dysregulation of microRNAs (miRNAs) has a fundamental role in the initiation, development and progression of several human cancers, including breast cancer (BC), since strong evidence has shown that miRNAs can regulate the expression of oncogenes or tumor suppressor genes. A possible role of miRNAs in the diagnosis in BC has been demonstrated. As miRNAs has been found stable in biofluids, extracellular multiple miRNA profiles have been proposed as diagnostic tools, showing better diagnostic performance than individual miRNAs in BC. In this paper, based on the current literature, we present the role of microRNAs in the diagnosis and therapy monitoring of BC. Furthermore, we report new miRNA-based drugs that could be turned into promising therapy for BC, alone or in combination with conventional therapy. We also discuss how extracellular miRNAs could become new, easily accessible, affordable, non-invasive tools for BC patients.