MicroRNA在乳腺癌转移中的作用

MicroRNAs(miRNAs)是一类内源性小分子RNA,在转录后水平抑制基因的表达。研究表明多种miRNAs在包括乳腺癌在内的多种肿瘤中扮演着癌基因或者抑癌基因的角色,并且在肿瘤发生发展的各个阶段都有特定的miRNAs参与。本文综述了乳腺癌侵袭和转移过程中相关的miRNAs的作用。     

microRNAs与乳腺癌

microRNAs（miRNAs）是一类长约21~24个核苷酸的小分子非编码RNA,通过与位于靶基因mRNA 3' UTR区域的特异性结合位点互补配对结合,促进靶基因mRNA的降解和/或抑制翻译过程,从而行使调节基因表达的功能。miRNAs广泛存在于真核细胞内,参与了细胞的分化、增殖、凋亡、周期调控、迁移以及肿瘤的发生发展等多种生物学进程。miRNAs表达谱是一类潜在的强有力的评估肿瘤发生、发展、诊断、治疗及预后的生物学指标,在人类肿瘤的不同类型中均存在显著差异。乳腺癌是女性最常见的恶性肿瘤之一,不同类型的乳腺癌组织中miRNAs的表达谱也不同。本文对目前为止发现的一些与乳腺癌发生发展、转移及治疗反应等相关的miRNAs及其下游靶基因在乳腺癌中的表达及作用进行综述。      

MicroRNAs在乳腺癌干细胞中的作用研究进展

乳腺癌干细胞（breast cancer stem cells,BCSCs）是导致乳腺癌发生、转移、耐药、复发等的重要原因。MicroRNAs（miRNAs）是近年来发现的一种非编码小分子RNA,可通过与靶标基因的3 '-非翻译区（3'-UTR）的完全或不完全配对,抑制靶标基因的翻译或降解靶标基因,从而发挥多种生物学功能。miRNAs在BCSCs中的异常表达可调控BCSCs的自我更新、抗凋亡、上皮间质转化（epithelial-mesenchymal transition,EMT）等生物学行为,从而促进乳腺癌的复发、转移。以miRNAs为研究靶点,为乳腺癌的诊断、预后及治疗提供了全新的思路。本文就近年来该方面的研究进展简要综述。     

MicroRNAs在乳腺癌中作用的研究进展

MicroRNAs（miRNAs）是一类新发现的非编码RNA分子，通常在转录后水平调控基因表达，广泛参与细胞增殖、分化与凋亡等生命过程。据文献报道，有15种miRNAs位于人类乳腺癌相关断点区域。这表明，特定类型癌症中包括miRNAs在内的基因区域的缺失或获得都与恶性肿瘤的发生有关。miRNAs的表达变化及其对靶基因的综合调控对乳腺癌的发生发展、特殊肿瘤表型的形成及预后等产生深远的影响。     

乳腺癌相关MicroRNAs研究进展

MicroRNAs(miRNAs)是一类广泛存在于真核细胞中长约18~23个核苷酸的小分子非编码RNA,具有转录后基因调控的功能,参与调节细胞的分化、增殖、凋亡、迁移等多种生物学进程.现今乳腺癌已成为女性常见的恶性肿瘤之一,但其发病病因尚未完全清楚.近年来,通过对分子生物学的研究,发现miRNAs是一类潜在的强有力的评估乳腺癌的发生、发展,诊断、治疗及预后的生物学指标.本文主要对miRNAs这一类新的肿瘤分子生物学标记物在乳腺癌中的作用机制作一综述.     

乳腺癌细胞与乳腺上皮细胞MicroRNAs表达谱的差异性分析

背景与目的：已有研究表明,MicroRNAs（miRNAs）的异常表达参与了乳腺癌的发生和发展,常起到抑癌基因或癌基因作用。本研究旨在探讨乳腺癌细胞与乳腺上皮细胞miRNAs的差异性表达,并预测异常表达的miRNAs可能调控的靶基因。方法：培养乳腺癌细胞株MCF-7和正常乳腺上皮细胞株HBL-100．分别提取细胞总RNA,并进行质检;利用miRNAs芯片技术,检测乳腺癌细胞和正常乳腺上皮细胞miRNAs的表达,对其表达谱进行差异性分析：采用实时定量RT—PCR进行验证：运用MiRanda、TargetScan、PicTar、DIANA—microT软件预测miRNAs可能调控的靶基因。结果：从MCF-7细胞与HBL-100细胞提取到的总RNA纯度较高,其A260／A280为1．90,A260/A230为2．0;琼脂糖凝胶实验结果显示总RNA完整性好。通过miRNAs表达谱的差异性分析,获得173个与乳腺癌相关的miRNAs,其中113个表达上调,60个表达下调：实时定量PCR检测到mir-18a和mir-195在MCF-7细胞中高表达;对乳腺癌细胞显著异常表达的mir-200b进行信息学分析,共筛选出68个靶基因。结论：获得了乳腺癌细胞与乳腺上皮细胞miRNAs的差异表达谱,其中部分miRNAs可能通过调控其靶基因而参与乳腺癌的发病机制。     

miR-485-5p在恶性肿瘤中的研究进展

MicroRNAs(miRNAs)是一类长度约22个核苷酸的非编码RNA,在基因表达调控中,参与多种重要的生理和病理过程。miRNAs能够特异性结合靶基因序列,抑制基因的转录或翻译,从而抑制基因在转录或转录后水平上的表达。miRNAs作为肿瘤抑制因子或促进因子在癌症发生发展中经常失调。最近的研究发现miR-485-5p在多种癌症中表达下调,并调控肿瘤细胞生长、增殖、侵袭和迁移。miR-485-5p在肿瘤诊断、治疗及预后相关方面可作为具有潜在价值的肿瘤标志物,并有望成为临床肿瘤靶向治疗的新的治疗靶点。本文围绕miR-485-5p在肝癌、胃癌、乳腺癌及其他恶性肿瘤中的研究进展展开综述并对其未来应用和发展进行展望。     

微小RNAs：乳腺癌重要的调控因子

微小RNAs（MicroRNAs,简称miRNAs）是长度为18～25个核苷酸的内源性非编码小分子RNA,通过剪切mRNA、调节靶基因、抑制蛋白质翻译,进而调控多种生物学行为,如发育进程、干细胞分化、细胞凋亡、疾病以及肿瘤的发生。本文将介绍miRNAs作为原癌基因或抑癌基因参与人类乳腺癌发生、发展及扩散转移的研究进展,并对人类现有miRNAs作为肿瘤基因诊治的应用情况作一简述。     

微小RNA研究进展

微小RNA(miRNA)是参与基因转录后水平调控的非编码小分子RNA.人类基因中大约有3%编码miRNAs,而编码蛋白的基因中30%受到miRNAs的调控.miRNAs在多种生物进程中起到关键作用,包括调节发育、细胞增殖、分化和凋亡,相应的miRNAs的表达变化与包括肿瘤在内的多种疾病有关.本文综述miRNAs的生物学及其与肿瘤的联系,并讨论了miRNAs的研究方法.     

miRNAs在三阴性乳腺癌多药耐药性中的研究进展

三阴性乳腺癌作为乳腺恶性肿瘤中最具侵袭性的类型,化学治疗是其主要而有效的治疗手段,但多药耐药性的产生仍是影响疗效的主要障碍。miRNAs是一种内生型的、非编码小RNAs,它作为一种潜在的致瘤因子或抑制因子,能靶向调节其目的基因从而参与肿瘤的耐药。因此,在开拓新的三阴性乳腺癌基因治疗的策略中,miRNAs具有潜在的治疗价值。本文总结了miRNAs在三阴性乳腺癌多药耐药中的作用机制及其在治疗中的应用前景。     

microRNA在乳腺癌诊断及预后判断中的作用

乳腺癌是全球女性患病率最高的恶性肿瘤,严重危害广大女性的健康。微小RNA(microRNA,miRNA)是一类小的内源性非编码RNA,通过与mRNA 3’端非翻译区部分互补配对,在翻译后水平调节靶基因的表达。miRNA在乳腺的发育过程中发挥多种作用,其表达异常可能导致乳腺癌的发生。乳腺癌中miRNA的异常表达,以及miRNA在血清中的稳定存在,使miRNA有望成为新的生物标志物用于乳腺癌的诊断及预后判断。     

Metastasis-related miRNAs,active players in breast cancer invasion,and metastasis

Breast cancer is the most common malignancy with the highest incidence among women in the world. Metastasis is the major reason for breast cancer-related deaths. The precise molecular circuitry that governs the metastasis process has not been completely understood. Discoveries of microRNAs (miRNAs) open a new avenue for cancer metastasis research. It has become clear that alterations of miRNA expression contribute to cancer pathogenesis. miRNAs control a wide array of physiological and pathological processes, including development, differentiation, cellular proliferation, programmed cell death, oncogenesis, and metastasis by modulating the expression of their cognate target genes through cleaving mRNA molecules or inhibiting their translation. Some miRNAs are associated with the invasive and metastatic phenotype of breast cancer cell lines or identified in metastatic tumor tissues and lymph nodes. Some miRNAs serve as metastasis suppressors and their expression is frequently downregulated or lost in both breast cancer cell lines and metastatic foci. Some miRNAs are considered to play key roles in the phenotype formation of breast cancer stem cells. This review will focus on recent discoveries related to the miRNAs involved in the metastasis of breast cancer and discuss the implications for the diagnosis, prognosis, and therapeutic strategies of breast cancer.     

The roles of oncogenic miRNAs and their therapeutic importance in breast cancer

Since the discovery of tumour suppressive miRNA in 2002, the dysregulation of miRNAs was implicated in many cancers, exhibiting both tumour suppressive and oncogenic roles. Dysregulation of miRNAs was found to be involved in the initiation of oncogenesis, as well as the progression, invasion and metastasis of cancers. While normal miRNA inhibitory functions help regulate gene expression in the cell, oncogenic miRNA, when dysregulated can lead to suppression of critical pathways that control apoptosis, cell cycle progression, growth and proliferation. This suppression allows for the upregulation of pro-oncogenic factors that drive cell survival, growth and proliferation. Due to emerging discoveries, oncogenic miRNAs are proving to be a critical component in cancers, such as breast cancer, and may provide novel avenues for cancer treatment. In this article, we discuss the roles of the most studied oncogenic miRNAs in breast cancer including clusters and families involved as well as the less studied and recently discovered oncogenic miRNAs. These miRNAs provide valuable information into the complexity of regulatory elements affected by their overexpression and the overall impact in the progression of breast cancer. Also, identifying miRNAs causing or leading to resistance or sensitivity to current anti-cancer drugs prior to treatment may lead to an improvement in treatment selection and overall patient response. This review summarizes known and recently discovered miRNAs in literature found to have oncogenic roles in breast cancer initiation and the progression, invasion and metastasis of the disease.     

MicroRNA-regulated gene networks during mammary cell differentiation are associated with breast cancer

MicroRNAs (miRNAs) play pivotal roles in stem cell biology, differentiation and oncogenesis and are of high interest as potential breast cancer therapeutics. However, their expression and function during normal mammary differentiation and in breast cancer remain to be elucidated. In order to identify which miRNAs are involved in mammary differentiation, we thoroughly investigated miRNA expression during functional differentiation of undifferentiated, stem cell-like, murine mammary cells using two different large-scale approaches followed by qPCR. Significant changes in expression of 21 miRNAs were observed in repeated rounds of mammary cell differentiation. The majority, including the miR-200 family and known tumor suppressor miRNAs, was upregulated during differentiation. Only four miRNAs, including oncomiR miR-17, were downregulated. Pathway analysis indicated complex interactions between regulated miRNA clusters and major pathways involved in differentiation, proliferation and stem cell maintenance. Comparisons with human breast cancer tumors showed the gene profile from the undifferentiated, stem-like stage clustered with that of poor-prognosis breast cancer. A common nominator in these groups was the E2F pathway, which was overrepresented among genes targeted by the differentiation-induced miRNAs. A subset of miRNAs could further discriminate between human non-cancer and breast cancer cell lines, and miR-200a/miR-200b, miR-146b and miR-148a were specifically downregulated in triple-negative breast cancer cells. We show that miR-200a/miR-200b can inhibit epithelial-mesenchymal transition (EMT)-characteristic morphological changes in undifferentiated, non-tumorigenic mammary cells. Our studies propose EphA2 as a novel and important target gene for miR-200a. In conclusion, we present evidentiary data on how miRNAs are involved in mammary cell differentiation and indicate their related roles in breast cancer.     

MicroRNA在乳腺癌中作用的研究进展

MicroRNA（miRNA,miRNAs)是广泛存在于生物中,长度约为20-24个核苷酸的非编码微小RNA分子。目前研究发现,miRNA与肿瘤的发生、进展有紧密联系,且逐渐成为癌症研究的热点。近年来,miRNA在乳腺癌发生与进展中起到的重要作用逐渐被揭示,已迅速发展为乳腺癌等癌症的重要生物标记物。本综述将就微小RNA在乳腺癌的发生、进展、远处转移、早期诊断以及化学治疗耐药性方面的作用进行论述。