miRNA与乳腺癌发生发展和多药耐药的研究现状

目的:总结近期国内外有关微小RNA(miRNA)在乳腺癌发生发展和多药耐药中作用的研究进展。方法:应用Pubmed和CNKI期刊全文数据库检索系统,以"miRNA、乳腺癌耐药和耐药相关蛋白"为关键词,检索2008-01-2011-03有关miRNA在乳腺癌发生发展和多药耐药中作用的文献。纳入标准:1)miR-NA在乳腺癌发生发展中的作用。2)miRNA通过调控耐药蛋白表达参与乳腺癌多药耐药。根据纳入标准分析33篇文献。结果:多种miRNA与乳腺癌的发生发展及侵袭转移和复发密切相关。其中,能够促进乳腺癌侵袭转移的miRNA少有报道,目前仅有miR-373和miR-21。多种miRNA能够抑制乳腺癌侵袭转移,如:miR-340、miR-1258、miR-520b、miR-206、miR-19、miR-34和miR-199a/b。此外,多种miRNA参与乳腺癌多药耐药的形成过程。其中,miR-519c、miR-328和miR-520h3种miRNA可调控乳腺癌耐药蛋白(BCRP)表达,miRNA-451可调控P糖蛋白(P-gp)表达,miR-326可调控多药耐药相关蛋白(MRP)表达从而参与乳腺癌多药耐药。结论:深入研究miRNA在乳腺癌发生及多药耐药中的作用将为乳腺癌的治疗提供新的有效靶点。     

微RNA-27a在乳腺癌中的研究进展

微RNA(miRNA)是新型基因表达调控小分子，其对肿瘤的调控作用在近年来的研究中备受肯定。miRNA-27a为miRNA家族中的重要成员，高表达于乳腺癌组织中，导致患者预后不良。miRNA-27a能够调控乳腺癌瘤体的血管生成以及乳腺癌细胞的增殖、侵袭和转移等多种生物学行为。此外，其还与乳腺癌的诊断、治疗密切相关。笔者就其在乳腺癌中的研究进展作一综述，以期为乳腺癌的诊断、治疗及预后判断提供新的思路。     

miRNA对肿瘤生物学特性的影响

研究显示miRNA与肿瘤发生形成过程及其恶性生物学行为密切相关,作为一种调节分子可能参与了肿瘤的发生以及肿瘤细胞的增殖、分化、细胞凋亡、侵袭和转移及肿瘤耐药等的调节.miRNA靶标及其作用机制的深入研究可为解开肿瘤的发生发展机制及肿瘤治疗策略提供新的思路.     

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.     

miRNA在乳腺癌中作用的研究进展

microRNA(miRNA)是一类内源性的、进化上高度保守的非编码小分子RNA.miRNA不仅参与正常细胞的生长及信号转导过程,也参与肿瘤细胞的生物调控过程.随着相关研究的深入,miRNA在乳腺癌发生中的作用逐渐被揭示,已成为探寻乳腺癌发生和发展机制的重要研究靶点.     

MicroRNAs的研究方法学及其与肿瘤发生发展关系的研究进展

MicroRNAs（miRNAs）是一类新的、非编码的、内源性小RNAs,可以通过抑制蛋白质翻译、剪切mRNA调节靶基因的表达。通过应用RNA反义抑制剂、点突变、转基因和特异性引物,研究特定miRNA在肿瘤发生中的作用;应用Northern blotting分析、Real-time PCR、miRNA芯片比较表达谱差异,了解特异性miRNAs的表达是上调还是下调,可以对miRNA在肿瘤发生中的作用进行研究。越来越多的研究表明,miRNAs参与了包括肝癌、肺癌、乳腺癌、结肠癌、脑肿瘤及白血病在内的多种肿瘤的发生、发展。MiRNAs在肿瘤发生、发展中的作用主要表现为3个方面：①有些miRNA基因可能起着癌基因的作用,调节细胞的增殖、凋亡;②有些miRNA基因则可能起到抑癌基因的作用;③一些致瘤病毒编码的miRNA也可能参与相关肿瘤的发生,细胞miRNA可能在致瘤病毒生命活动周期中扮演重要角色,而病毒自身为了在宿主细胞中成功存活,也必定会反过来调节细胞miRNA的表达,参与肿瘤发生。     

miRNA与肿瘤侵袭转移

目前,microRNA (miRNA)已成为肿瘤研究中最基本的参与者,主要通过与靶标基因3 'UTR(非翻译区)的完全或不完全配对,降解靶标基因mRNA或抑制其翻译,从而参与调控个体发育、细胞凋亡、增殖及分化等生命活动.miRNA作为调控基因表达的重要分子在肿瘤侵袭转移中的作用越来越受到重视,表明miRNA在肿瘤侵袭和转移中的作用机制具有重要的理论意义,同时也可为肿瘤的诊断和治疗提供新方法.本文就miRNA通过调控上皮间质转化及肿瘤干细胞导致肿瘤侵袭转移的最新研究进展作一综述.     

乳腺癌相关microRNA的研究进展

乳腺癌作为一种复杂的、表型多样性的遗传性疾病，涉及基因表达和各种结构的变化。如何早期诊断乳腺癌，降低乳腺癌发病率、死亡率一直是大众关注的焦点。微小RNA（microRNA）是一类内源性非编码单链RNA，广泛参与乳腺癌细胞的增殖、分化、凋亡等生理过程，并与乳腺癌患者的临床分期、淋巴结转移、远处转移等相关。现就microRNA在乳腺癌发生、发展过程中的作用，及其在该病诊疗过程中的应用作一综述，以期为乳腺癌的进一步研究提供新的思路。     

乳腺癌miRNA的研究进展

研究显示微小RNA(miRNA)与乳腺癌的发生发展过程关系密切.多种miRNA参与了乳腺癌的发病进展,并能评估预后,指导临床用药及探索其耐药机制.     

微小RNA在乳腺癌耐药中的研究

乳腺癌的多药耐药(MDR)是造成乳腺癌治疗失败的关键因素.微小RNA (miRNA)是一种内源性表达小分子单链RNA,通过与靶基因的信使RNA结合调控基因的转录后表达.miRNA参与乳腺癌耐药形成的多种机制,是治疗耐药乳腺癌的可行靶点.寻找新的miRNA并研究其在乳腺癌耐药中的作用已成为当今研究的热点.     

微小RNA与乳腺癌生物学行为的关系

MicroRNA (miRNA) controls the proliferation of breast cancer cells in many ways such as cell apotosis, cell cycle and methyltransferase. Also, it controls the metastasis of breast cancer cells in many ways such as microenvironment, epithelial-mesenchymal transition and vessel formation. Large amounts of recent studies indicate that miRNAs are specifically expressed in breast cancer tissue and play important roles in proliferation, metastasis and treatment of breast cancer.     

MicroRNA-30a inhibits cell migration and invasion by downregulating vimentin expression and is a potential prognostic marker in breast cancer

Tumor recurrence and metastasis result in an unfavorable prognosis for cancer patients. Recent studies have suggested that specific microRNAs (miRNAs) may play important roles in the development of cancer cells. However, prognostic markers and the outcome prediction of the miRNA signature in breast cancer patients have not been comprehensively assessed. The aim of this study was to identify miRNA biomarkers relating to clinicopathological features and outcome of breast cancer. A miRNA microarray analysis was performed on breast tumors of different lymph node metastasis status and with different progression signatures, indicated by overexpression of cyclin D1 and β-catenin genes, to identify miRNAs showing a significant difference in expression. The functional interaction between the candidate miRNA, miR-30a, and the target gene, Vim, which codes for vimentin, a protein involved in epithelial-mesenchymal transition, was examined using the luciferase reporter assay, western blotting, and migration and invasion assays. The association between the decreased miR-30a levels and breast cancer progression was examined in a survival analysis. miR-30a negatively regulated vimentin expression by binding to the 3'-untranslated region of Vim. Overexpression of miR-30a suppressed the migration and invasiveness phenotypes of breast cancer cell lines. Moreover, reduced tumor expression of miR-30a in breast cancer patients was associated with an unfavorable outcome, including late tumor stage, lymph node metastasis, and worse progression (mortality and recurrence) (p < 0.05). In conclusion, these findings suggest a role for miR-30a in inhibiting breast tumor invasiveness and metastasis. The finding that miR-30a downmodulates vimentin expression might provide a therapeutic target for the treatment of breast cancer.     

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.     

MicroRNA-mediated breast cancer metastasis: from primary site to distant organs

The recent upsurge of interest in microRNA (miRNA) is partly attributed to the discovery of the novel roles of miRNAs in many physiological and pathological processes, including tumor development. Research on breast cancer metastasis has also focused on the concept of miRNA, which can act either as promoters or as suppressors of metastases. This review will focus on a series of recent studies that demonstrate the involvement of miRNAs in breast cancer metastasis and will briefly describe various pathways of miRNA-regulated metastasis. Finally, future prospects will be discussed for the potential role of miRNAs as predictive markers and therapeutic agents for patients with breast cancer metastases.     

MicroRNA-4472 Promotes Tumor Proliferation and Aggressiveness in Breast Cancer by Targeting RGMA and Inducing EMT

BackgroundBreast cancer is the most common cause of cancer-related death in women worldwide. MicroRNA (miRNA) ectopic expression has been reported to be involved in the regulation of gene expression in breast cancer. We screened several differentially expressed miRNAs associated with breast cancer chemoresistance, growth, and metastasis using a miRNA microarray. Increased expression of miR-4472 has been associated with larger breast tumors and chemoresistance. However, the biologic function of miR-4472 and its molecular mechanisms in cancer progression have not yet been reported.Materials and MethodsReal-time quantitative polymerase chain reaction was used to measure the expression of miR-4472 in breast cancer tissue and cell lines. The biologic functions of miR-4472 and its target gene were explored using Transwell, cell proliferation, and flow cytometry assays. Bioinformatics tools, dual-luciferase reporter assays, and Western blot were used to identify the target genes of miR-4472. Western blot was used to explain the participation of miR-4472 and target gene in epithelial-to-mesenchymal transition.ResultsmiR-4472 was significantly upregulated in highly metastatic breast cancer tissues, and its expression was positively associated with larger tumor size and advanced pTNM stage. miR-4472 promoted breast cancer cell metastasis and growth. Repulsive guidance molecule A (RGMA) was a direct target gene of miR-4472. RGMA was identified as a suppressor in cancer metastasis. miR-4472 downregulated expression of RGMA and promoted epithelial-to-mesenchymal transition by suppressing E-cadherin and initiating vimentin, β-catenin, and Slug.ConclusionsmiR-4472 contributes to the progression of breast cancer by regulating RGMA expression and inducing epithelial-to-mesenchymal transition, indicating that miR-4472/RGMA might serve as a therapeutic target for breast cancer.     

lncRNA/miRNA在胰腺癌发生发展中的研究进展

ncRNA/miRNA在多种实体肿瘤中表达异常，参与肿瘤的增殖、侵袭、转移。胰腺癌是发病率较高、死亡率高的恶性肿瘤，通过深入研究lncRNA/miRNA在胰腺癌发生发展中的分子机制，可为胰腺癌的治疗提供新的靶点。     

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.     

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.     

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。