miRNA调控肿瘤多药耐药的研究进展

耐药导致肿瘤化疗失败的分子机制至今尚未完全阐明.多项研究发现miRNA广泛参与了肿瘤增殖、转移、凋亡等多个生物学过程.近年来研究证实,miRNA在多种肿瘤耐药过程中发挥重要调节作用.通过阅读文献,本文旨在汇总miRNA调控肿瘤耐药的分子机制.     

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。     

乳腺癌化疗耐药中肿瘤干细胞的作用及其机制

目的:了解肿瘤干细胞在乳腺癌化疗耐药中的作用及其相关机制的研究进展。方法:应用检索Pubmed及CNKI数据库检索系统,以肿瘤、干细胞、乳腺癌、化疗和耐药等为关键词,检索1999-01-2011-05的相关文献,纳入标准:肿瘤干细胞与乳腺癌化疗耐药。根据纳入标准分析42篇文献。结果:肿瘤干细胞是导致乳腺癌化疗耐药和治疗失败的主要细胞,其耐药的机制包括ATP结合盒转运子的过度表达、细胞解毒酶的过度活化、细胞存活和凋亡相关信号转导通路的异常激活、肿瘤壁龛对肿瘤干细胞的保护作用以及大部分肿瘤干细胞处于静止期。通过对这些耐药机制的干预,可以逆转肿瘤干细胞的耐药性。结论:肿瘤干细胞是导致乳腺癌化疗耐药的关键细胞,对其耐药机制的研究有助于展开针对肿瘤干细胞的靶向治疗,改善患者的预后。     

microRNA在乳腺癌耐药中的作用

乳腺癌是危害全球女性健康的主要疾病,而乳腺癌患者对现有治疗方法产生获得性耐药成为目前乳腺癌临床治疗所面临的难题.微小RNA (miRNA)是一种内源性的非编码RNA,它参与调控多种生物学过程,包括细胞增殖、侵袭、转移、上皮间质转化和耐药等.获得性耐药包含多种复杂机制,可通过特定miRNA的异常表达影响细胞相关蛋白的表达、抗肿瘤药物与相应靶点的结合以及凋亡相关途径引起乳腺癌耐药.本文将重点关注在乳腺癌内分泌治疗、化疗、分子靶向治疗发生获得性耐药中表达异常的miRNA.相信miRNA能够成为乳腺癌临床诊断与治疗以及对抗获得性耐药的生物标志物和新的治疗靶点.     

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.     

MicroRNA在乳腺癌内分泌耐药中的研究新进展

内分泌治疗可显著改善雌激素受体阳性的乳腺癌患者的无病生存期和总生存期,但内分泌耐药是导致治疗失败的重要原因。微小RNA（microRNA,miRNA）是肿瘤研究领域中的热点,新近研究证实miRNA的表达变化是乳腺癌耐药机制之一。miRNA通过上调药物外排转运、抗凋亡蛋白、调节多药耐药信号传导网络等方式促成上皮 间质转化并形成肿瘤干细胞。miRNA亦可能通过调节雌激素受体α表达、受体酪氨酸激酶信号传导、细胞生存信号及细胞凋亡等途径引发耐药。miRNA可能成为激素受体阳性乳腺癌的预后因子、内分泌治疗疗效评估的预测因子以及新的靶点。     

单细胞测序在三阴性乳腺癌新辅助化疗中的应用研究进展

三阴性乳腺癌是最具侵袭性、恶性程度最高的乳腺癌类型,目前多采用以化疗为主的综合治疗方案,新辅助化疗在其中发挥重要作用,但近半数患者会出现耐药,而具体机制尚不明确。单细胞测序技术能够在单个细胞基础上精准评估肿瘤发生、发展过程中基因组、转录组和表观遗传学信息的改变,为明确诊断肿瘤亚型、了解肿瘤耐药机制、发现治疗新靶点、评估疗效与预后等提供有力工具,在三阴性乳腺癌的新辅助化疗中具有广阔的应用前景。     

microRNAs与ABC转运蛋白介导的肿瘤多药耐药研究进展

目的回顾ABC转运蛋白与肿瘤耐药的研究现状,探讨miRNA在逆转肿瘤耐药过程中的作用机制。方法应用PubMed和CNKI期刊全文数据库检索系统,检索2010-01-01-2014-05-20的相关文献,以"ABC转运蛋白、miRNA和多药耐药"为关键词。纳入标准:1)ABC转运蛋白的表达水平与肿瘤耐药;2)miRNA对ABC转运蛋白表达水平的调控;3)miRNA对肿瘤细胞药物敏感性的影响,根据纳入标准符合分析的文献34篇。结果大多数癌症患者使用一种化疗药物治疗后,肿瘤细胞可能因为种种原因,不仅对该药产生耐药,而且对多种结构不同和作用机制完全不同的其他药物也产生交叉耐药。研究表明,在多药耐药导致肿瘤化疗失败的众多原因中,ABC转运蛋白过表达是导致肿瘤多药耐药的主要原因之一。在耐药肿瘤细胞当中高表达的ABC转运蛋白主要有乳腺癌耐药蛋白ABCG2,多药耐药相关蛋白ABCC1,P-糖蛋白ABCB1,这些蛋白采用ATP水解的能量将细胞内药物泵出细胞外,从而降低细胞内药物的浓度,使细胞产生耐药性。miRNA能与ABC转运蛋白mRNA的3′UTR结合,使mRNA降解或抑制其翻译,导致目标蛋白的表达受到抑制,从而增加肿瘤细胞的药物敏感性,逆转由ABC转运蛋白过表达引起的肿瘤多药耐药。结论 miRNA可以逆转由ABC转运蛋白家族高表达所引起的肿瘤耐药,这为肿瘤多药耐药的研究提供了新的思路。     

miRNA在胶质瘤化疗耐药中的研究进展

化疗现作为胶质瘤的常规治疗手段之一,对改善病人的预后起了重要的作用,而耐药是化疗失败的常见原因。胶质瘤化疗耐药的机制很复杂,包括DNA甲基化,基因突变等。microRNA(miRNA)是一类非编码的内源性小分子RNA,进化上保持高保守性,对基因表达进行转录后水平的调控。国内外学者对miRNA在肿瘤耐药中的作用做了积极的探索,发现miRNA在其中起十分重要的作用。本文对胶质瘤耐药相关的miRNA进行综述。     

miRNA对肺癌化疗耐药调控研究进展

目的:总结miRNA对肺癌耐药调控的研究状况,并探讨其在预测肺癌对药物敏感性和耐药性中的作用。方法:应用PubMed及CNKI期刊全文数据库检索系统,以"miRNA和肺癌"等为关键词,检索2007-01-2013-01的相关文献,共检索到英文文献732篇,中文文献88篇。纳入标准:1)肺癌耐药相关机制;2)miRNA在肺癌耐药中的作用;3)miRNA预测肺癌细胞的药物敏感性。根据纳入标准,符合分析的文献33篇。结果:肺癌耐药机制包括药物吸收降低或排出增多、药物靶点改变、细胞修复功能增强及细胞凋亡的减弱等,涉及药物作用各个环节关键基因突变可能导致耐药发生。而miRNA为一类高度保守的非编码RNAs,通过对上述各环节关键基因表达的调控进而调节肺癌细胞对化疗药物的敏感性。在肺癌化疗耐药的患者中,肺癌细胞miRNA突变或表达异常,导致miRNA对靶基因如药物转运相关基因、细胞解毒功能相关基因、细胞损伤后自我修复能力相关基因、细胞凋亡相关基因及肿瘤上皮间质化相关基因等表达的异常调控,致使肺癌细胞化疗耐药产生。同时,根据这些miRNA表达情况可预测肺癌患者对药物的反应。结论:miRNA对肺癌细胞耐药调控发挥着重要作用,从而为肺癌化疗耐药预测提供了新的思路和手段。     

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。     

MicroRNA in HCC: Biomarkers and Therapeutic Targets

Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. At present, diagnostic methods such as imaging observation, serum testing and tissue biopsy, as well as treatment methods such as surgical resection, radiotherapy, and chemotherapy have certain limitations in clinical interventions for HCC due to the complex pathogenesis and drug resistance of liver cancer, which seriously affect the survival and prognosis of patients. As a large-scale cytokine, microRNA (miRNA) plays an important role in regulating various life activities of cells. Extensive evidence proved that certain miRNAs are specifically expressed in the tissues and blood of HCC patients, and some of them have been confirmed as important factors that can participate in the regulation of key signaling pathways in cancer cells. For this reason, these miRNAs have great potential in clinical diagnosis and treatment of HCC, and can improve the limitations of conventional diagnosis and treatment. Our paper reviews the research on miRNA biomarkers and targets in HCC in recent years, and aims to provide new ideas for the diagnosis and treatment of HCC.     

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 expression profile of MCF-7 human breast cancer cells and the effect of green tea polyphenon-60

This study reports for the first time the microRNA expression profile of human breast cancer MCF-7 cells and the effect of green tea. Although hundreds of miRNAs have been identified in humans, only a small proportion (25.6%) of miRNAs are expressed in MCF-7 cells. Low concentration treatment with Polyphenon-60 significantly alters the miRNA expression profile in MCF-7 cells. Twenty three miRNAs have been identified with differential expression after a 48 h treatment with 10 μg/ml Polyphenon-60 (green tea extract). These miRNAs include miR-21 and miR-27 that were found to be down-regulated following treatment with green tea. These two miRNAs have previously been identified as being overexpressed in MCF-7 breast cancer cells, with miR-21 specifically implicated in down-regulating the tumor suppressor gene, tropomyosin-1. This data supports the hypothesis that Polyphenon-60-induced modification of the breast cancer miRNA expression profile contributes to the efficacy of green tea treatment. The resulting decrease in carcinogenesis is further supported by the altered miRNA regulation of potential oncogenes and tumor-suppressor genes.     

Regulation of epithelial-mesenchymal transition through microRNAs: clinical and biological significance of microRNAs in breast cancer

Breast cancer is a malignant disease to treat among female worldwide due to its high capability to metastasize and mutate. Epithelial-mesenchymal transition is one of the essential processes involved in the metastatic capacity of breast cancer. In the recent time, the studies demonstrate that microRNAs, a kind of small non-coding RNA molecules, could be served as negative regulators in breast cancer, regulating cell cycle, drug resistance, and the process of metastasis in cancer development. With the assistance of microRNA profiling, the study concentrating on the regulatory function of miRNAs in breast cancer could be investigated more effectively and efficiently. More recent studies demonstrate that miRNAs have an important role to play in the EMT process of breast cancer to modulate metastasis. This small essay is on the purpose of demonstrating the significance and detection of miRNAs in breast cancer EMT process as oncogenes and tumor suppress genes through miRNA profiling according to the reports mainly in the recent 5 years, providing the evidence of efficient target therapy and effective pro-diagnosis focusing on miRNAs expression of breast cancer patients.     

Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non-small cell lung cancer

Studies have shown cell-free microRNA(miRNA) circulating in the serum and plasma with specific expression in cancer,indicating the potential of using miRNAs as biomarkers for cancer diagnosis and therapy.This study was to investigate whether plasma miRNA-21(miR-21) can be used as a biomarker for the early detection of non-small cell lung cancer(NSCLC) and to explore its association with clinicopathologic features and sensitivity to platinum-based chemotherapy.We used real-time RT-PCR to investigate the expr...     

肿瘤干细胞与microRNA的研究进展

肿瘤干细胞是肿瘤的起源性细胞, 具有高度的致瘤性和耐药性。微小RNA(microRNA或miRNA)是由21~25个核苷酸组成的内源性非编码单链RNA, 是基因表达调控因子, 参与许多生物功能的调节。最近的研究发现, microRNA参与肿瘤干细胞的分化、自我更新等生物学特性的调控。肿瘤干细胞和microRNAs可以作为肿瘤研究的一个新的切入点。本文就近年来的研究进展做简要综述。      

The histone deacetylase inhibitor trichostatin A alters microRNA expression profiles in apoptosis-resistant breast cancer cells

The development of drug resistance represents a major complication in the effective treatment of breast cancer. Epigenetic therapy, through the use of histone deacetylase inhibitors (HDACi) or demethylation agents, is an emerging area of therapeutic targeting in a number of ontological entities, particularly in the setting of aggressive therapy-resistant disease. Using the well-described HDAC inhibitor trichostatin?A (TSA) we demonstrate the suppression of in?vitro clonogenicity in the previously described apoptosis-resistant MCF-7TN-R breast carcinoma cell line. Additionally, recent work has demonstrated that these agents can alter the expression profile of microRNA signatures in malignant cells. Using an unbiased microRNA microarray analysis, changes in miRNA expression of MCF-7TN-R cells treated with TSA for 24?h were analyzed. We observed significant up-regulation of 22 miRNAs and down-regulation of 10 miRNAs in response to TSA treatment. Our results demonstrate that the HDACi, TSA, exerts anticancer activity in the apoptosis-resistant MCF-7TN-R breast carcinoma cell line. This activity is correlated with TSA alteration of microRNA expression profiles indicative of a less aggressive phenotype.