MicroRNA在卵巢癌诊疗中的作用

微小RNA(micro RNA,miRNA)是一类长度约为22个核苷酸的单链非编码RNA,参与调节体内基因的表达,通过诱导靶mRNA的降解达到沉默的目的.目前大量研究表明多种miRNA与卵巢癌的诊断、预后以及化疗药物耐药中起到重要作用.全文对miRNA在卵巢癌中的多种作用进行总结,为临床找寻新的分子标志物提供科学依据.     

微小RNA在卵巢癌中的作用

微小RNA( miRNA)在卵巢癌中表达明显改变.基于微阵列芯片检测的卵巢癌相关miRNA表达谱和后续的对个别miRNA的深入研究,发现其与卵巢癌的发生、发展、复发、耐药等密切相关,有望用于卵巢癌早期诊断、复发检测、预后判定及治疗.     

MiR-200家族在卵巢癌中的研究进展

摘 要：微小RNA（miRNA）是一种内源性的、长约22个核苷酸的非编码小 RNA。通过在转录后水平降解靶 mRNA或者抑制靶基因的表达而参与调控细胞的生长、增殖和凋亡等。研究表明miR-200家族与卵巢癌发展、转移、耐药及预后密切相关,有望为卵巢癌的诊治提供新的思路。全文就miR-200家族在卵巢癌中作用的研究进展进行综述。     

miR-25在非小细胞肺癌中的研究进展

microRNA(微小RNA,miRNA)是小的非编码RNA,能够通过靶向信使RNA进行翻译抑制或在较小程度上降解来抑制基因表达。miRNA不受控制的表达与癌症进展相关,并且miRNA上调或下调与癌症中的致癌和肿瘤抑制作用相关。 miR-25是miRNA的一员,研究表明miR-25参与非小细胞肺癌的发生、转移侵袭、诊断、介导铂耐药及预后过程。本文主要综述了近年来非小细胞肺癌与miR-25相关研究取得的最新进展。     

miR-10a-5p基因甲基化对卵巢癌铂类耐药的影响

目的 卵巢癌是死亡率最高的妇科肿瘤,较强的化疗耐药性是其预后差的主要原因之一,为了阐明卵巢癌对铂类药物的耐药机制,本研究探讨miRNA基因的甲基化水平对卵巢癌铂类耐药的影响.方法 将卵巢癌组织分为敏感组和耐药组,每组各3例;采用基因芯片技术,对比分析了两组微RNA(microRNA,miRNA)的表达差异;采用实时荧光定量PCR,分别在6例敏感和3例耐药组织、铂类药物敏感(CoC1)和耐药的卵巢癌细胞系(CoC1/DDP),检测了候选miRNA的表达差异;应用Massarray技术,检测敏感组织(15例)与耐药组织(6例)中miRNA基因启动子的甲基化差异;应用生物信息学分析,鉴定目标miRNA的潜在靶基因.结果 以铂类药物敏感的卵巢癌组织样本为对照,利用基因芯片筛选,鉴定了6条在耐药组织样本中出现表达上调的miRNA(miR-493-3p、miR-10a-5 p、miR-16-2-3p、miR-1248、miR-451a、miR-628-3p)和6条表达下调的miRNA(miR-509-3p、miR-1197、miR-376a-3p、miR-1273a、miR-550a-3p、miR-19b-3p).组织验证发现,miR-509-3p、miR-493-3p、miR-10a-5p、miR-16-2-3p和miR-451a,与芯片结果一致;培养细胞研究发现,4条miRNA的表达调控方式与组织芯片结果一致,miR-10a-5p、miR-16-2-3p、miR-1248和miR-628-3p在耐药细胞系中高表达.进一步研究发现,与敏感肿瘤组织相比,耐药组织中miR-10a-5p基因启动子的甲基化水平出现显著降低,P=0.04.结合生物信息学预测HOXA1和USF2为miR-10a-5p与耐药相关的靶基因.结论 与敏感组相比,耐药组miR-10a-5p基因启动子甲基化水平显著降低,miR-10a-5p表达升高,通过抑制 HOXA1和USF2,抑制细胞凋亡,导致铂类化疗药物耐受.     

卵巢癌耐药相关微小RNA的研究进展

越来越多的证据表明,微小RNA(miRNA)的异常表达与肿瘤发生发展、转移及预后等密切相关.最近研究发现,异常表达的miRNA与卵巢癌化疗抵抗相关,提示miRNA将可能成为卵巢癌治疗的新靶点.进一步阐明miRNA与卵巢癌耐药的相关机制将有利于miRNA靶向治疗的研究.     

微小RNA与肿瘤耐药

微小RNA(miRNA)是近年来在真核生物中发现的、在转录后水平负调控基因表达的一类长约22个核苷酸的非编码小分子RNA.miRNA生物学效应广泛,与细胞生长、凋亡、新陈代谢和信号转导等密切相关.已报道miRNA在各种肿瘤中表达失常,可能发挥着癌基因和抑癌基因的双重作用,同时越来越多的研究表明miRNA在调节肿瘤细胞对抗肿瘤药物耐药方面发挥着重要作用.系统深入地研究miRNA在肿瘤耐药中的机制,将为发展基于miRNA逆转肿瘤耐药的治疗策略提供重要的依据.     

微小RNA与肿瘤耐药

微小RNA(miRNA)是近年来在真核生物中发现的、在转录后水平负调控基因表达的一类长约22个核苷酸的非编码小分子RNA.miRNA生物学效应广泛,与细胞生长、凋亡、新陈代谢和信号转导等密切相关.已报道miRNA在各种肿瘤中表达失常,可能发挥着癌基因和抑癌基因的双重作用,同时越来越多的研究表明miRNA在调节肿瘤细胞对抗肿瘤药物耐药方面发挥着重要作用.系统深入地研究miRNA在肿瘤耐药中的机制,将为发展基于miRNA逆转肿瘤耐药的治疗策略提供重要的依据.     

上皮性卵巢癌中microRNA的研究进展

非编码短序列RNA(microRNA,miRNA)是一类长度约为21～22个核苷酸的短序列、非编码、具有调控作用的单链RNA分子,可以在转录水平后调控mRNA的表达.作为一个重要的基因调节因子,miRNA在肿瘤中发挥癌基因或抑癌基因样作用,与肿瘤癌细胞的增殖、凋亡、转移、耐药等机制密切相关.卵巢癌是严重威胁女性健康的常见恶性肿瘤之一,在女性肿瘤中病死率居第5位,因病灶隐匿,不易早期发现,故发现时多为晚期,5年生存率低.随着miRNA在肿瘤中的深入研究,miRNA在卵巢癌中存在差异表达,其与卵巢癌的作用日渐明朗,有望成为新一代敏感的肿瘤标志物,并通过对其靶基因的研究,最终达到早期诊断及提高卵巢癌治疗效果的目的.     

卵巢上皮癌原发耐药相关microRNA的初步研究

目的 探讨难治性卵巢上皮癌耐药相关microRNA(miRNA),并预测其调控的靶基因,为进一步进行卵巢上皮癌耐药相关生物学通路研究提供基础.方法 收集接受满意肿瘤细胞减灭术的100例Ⅱb~Ⅲc期卵巢上皮癌患者的一般资料和组织学标本,根据术后化疗效果将患者分为铂类敏感组(n=91)和难治性卵巢癌组(n=9),每组各选取3例患者使用TaqMan Real-time PCR microRNA Array进行分析,得出差异表达的miRNA.根据靶基因预测网站的分析、miRNA及其靶基因在肿瘤中的研究,筛选出目标miRNA作为区分难治性卵巢癌组与铂类敏感组的标志物以待进一步研究.结果 miRNA表达谱芯片得到两组差异表达的miRNA共118个,其中难治性卵巢癌组与铂类敏感组相比,表达降低的miRNA有42个,表达升高的miRNA有76个.综合现有文献及靶基因预测网站分析,选取6个miRNA作为区分难治性卵巢癌组与铂类敏感组的目标miRNA.与铂类敏感组相比,miRNA-21和miRNA-27a在难治性卵巢癌组中表达明显升高(P﹤0.001),miRNA-100、miRNA-770-5p、miR-NA-200c和miRNA-497在难治性卵巢癌组中表达降低(P﹤0.05).结论 miRNA-21等118个miRNA可能与卵巢上皮癌耐药相关,miRNA-21、miRNA-27a的升高及miRNA-100、miRNA-770-5p、miRNA-200c、miRNA-497的降低可能提示卵巢上皮癌原发耐药.     

循环血液外泌体miRNA在卵巢癌发生发展中作用及其诊断价值的研究进展

卵巢癌（ovarian cancer,OC）是女性恶性肿瘤死亡的主要原因。由于卵巢癌无症状发展,缺乏早期诊断标志物,大多数患者在晚期才被诊断出来。早期检测卵巢癌可显著提高总生存率,在过去的几十年里,微小RNA（miRNA）在癌症的发展中起着重要的作用,因此引起了极大的关注。miRNA可以在循环血液中稳定存在(如包裹在外泌体中),并可通过外泌体的分泌和转移在肿瘤细胞之间和肿瘤细胞微环境的沟通中发挥重要的作用。此外,外泌体miRNA在卵巢癌中的表达是失调的,可能反映肿瘤的恶性特征。因此评估外泌体来源的循环miRNA可能会为卵巢癌提供一类新的非侵袭性生物标志物。本综述概述了有关外泌体miRNA在卵巢癌发生发展过程中的作用以及循环血液外泌体miRNA作为卵巢癌早期诊断潜在生物标志物的现状。     

微小RNA与肿瘤耐药

 【摘要】　微小RNA （miRNA）是近年来在真核生物中发现的、在转录后水平负调控基因表达的一类长约22个核苷酸的非编码小分子RNA。miRNA生物学效应广泛,与细胞生长、凋亡、新陈代谢和信号转导等密切相关。已报道miRNA在各种肿瘤中表达失常,可能发挥着癌基因和抑癌基因的双重作用,同时越来越多的研究表明miRNA在调节肿瘤细胞对抗肿瘤药物耐药方面发挥着重要作用。系统深入地研究miRNA在肿瘤耐药中的机制,将为发展基于miRNA逆转肿瘤耐药的治疗策略提供重要的依据。     

Differential patterns of microRNA expression in neuroblastoma are correlated with prognosis, differentiation, and apoptosis

Neuroblastoma accounts for 15% of pediatric cancer deaths, and although a few protein-coding genes, such as MYCN, are involved with aggressive pathogenicity, the identification of novel biological targets for therapeutic intervention is still a necessary prerequisite for improving patient survival. Expression profiling of 157 microRNA (miRNA) loci in 35 primary neuroblastoma tumors indicates that 32 loci are differentially expressed in favorable and unfavorable tumor subtypes, indicating a potential role of miRNAs in neuroblastoma pathogenesis. Many of these loci are significantly underexpressed in tumors with MYCN amplification, which have particularly poor prognoses. Interestingly, we found that miRNA expression levels substantially change in a MYCN-amplified cell line following exposure to retinoic acid, a compound which is well known for causing reductions in MYCN expression and for inducing neuroblastoma cell lines to undergo neuronal differentiation. We also show that small interfering RNA inhibition of MYCN by itself causes similar alterations in the expression of miRNA loci. In vitro functional studies of one locus, miR-184, indicate that it plays a significant role in apoptosis. The association of experimentally induced alterations of miRNA expression in neuroblastoma cell lines with differentiation or apoptosis leads us to conclude that these loci play important roles in neuroblastoma pathogenesis. We further suggest that MYCN may mediate a tumorigenic effect, in part, through directly or indirectly regulating the expression of miRNAs that are involved with neural cell differentiation and/or apoptosis, warranting substantial further studies of miRNAs as potential therapeutic targets.     

Epithelial–mesenchymal transition-associated miRNAs in ovarian carcinoma,with highlight on the miR-200 family: Prognostic value and prospective role in ovarian cancer therapeutics

MicroRNAs (miRNAs) are a family of short ribonucleic acids found to play a pivotal role in cancer pathogenesis. MiRNAs are crucial in cellular differentiation, growth, stress response, cell death and other fundamental cellular processes, and their involvement in ovarian cancer has been recently shown. They can repress the expression of important cancer-related genes and they can also function both as oncogenes and tumour suppressor genes. During epithelial–mesenchymal transition (EMT), epithelial cells lose their cell polarity and cell–cell adhesion and gain migratory and invasive properties. In the ovarian surface epithelium, EMT is considered the key regulator of the post-ovulatory repair process and it can be triggered by a range of environmental stimuli. The aberrant expression of the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) in ovarian carcinoma and its involvement in ovarian cancer initiation and progression has been well-demonstrated. The miR-200 family members seem to be strongly associated with a pathologic EMT and to have a metastasis suppressive role. MiRNA signatures can accurately distinguish ovarian cancer from the normal ovary and can be used as diagnostic tools to predict the clinical response to chemotherapy. Recent evidence suggests a growing list of new miRNAs (miR-187, miR-34a, miR-506, miRNA-138, miR-30c, miR-30d, miR-30e-3p, miR-370 and miR-106a, among others) that are also implicated in ovarian carcinoma-associated EMT, either enhancing or suppressing it. MiRNA-based gene therapy provides a prospective anti-tumour approach for integrated cancer therapy. The aim of nanotechnology-based delivery approach for miRNA therapy is to overcome challenges in miRNA delivery and to effectively encourage the reprogramming of miRNA networks in cancer cells, which may lead to a clinically translatable miRNA-based therapy to benefit ovarian cancer patients.