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.     

微小RNA与卵巢癌铂类耐药的研究进展

微小RNA(micmRNA,miBNA)是广泛存在于生物体内的一类非编码的小RNA,miRNA是细胞增殖、死亡、应激抗性和脂肪代谢的关键调节因素,体外实验已经证实miRNA在卵巢癌耐药中起重要作用.卵巢癌铂类耐药的产生与发展是十分复杂的过程,研究结果显示,miRNA的表达对卵巢癌细胞株的铂类药物敏感性有着重要作用,能够...     

微小RNA与肿瘤诊断

微小RNA (miRNA)能在转录后水平调节mRNA表达。miRNA与胃肠癌、肺癌、乳腺癌、卵巢癌、前列腺癌、胰腺癌和肝癌等多种肿瘤的发生、发展密切相关,而且很多miRNA在肿瘤中表达水平明显异常。miRNA可作为一种标志物用于多种肿瘤的诊断。     

微小RNA与肿瘤诊断

微小RNA（miRNA）能在转录后水平调节mRNA表达。miRNA与胃肠癌、肺癌、乳腺癌、卵巢癌、前列腺癌、胰腺癌和肝癌等多种肿瘤的发生、发展密切相关,而且很多miRNA在肿瘤中表达水平明显异常。miRNA可作为一种标志物用于多种肿瘤的诊断。     

卵巢上皮恶性肿瘤侵袭转移相关miRNA的筛选与鉴定

目的 探索与卵巢上皮恶性肿瘤侵袭转移可能相关的miRNA.方法 采用miRNA芯片,筛选SKOV-3ip和SKOV-3细胞差异表达miRNA.利用生物信息学软件TargetScan、MicroCosm、PicTar和GO,预测差异表达miRNA的靶基因及其功能.采用实时逆转录聚合酶链反应(real-time RT-PCR)技术,验证与卵巢癌侵袭转移可能相关的5种miRNA(let-7a、let-7e、let-7f、miR-22和miR-886-5p)在SKOV-3ip和SKOV-3细胞的表达.同时,检测这5种miRNA在另外一组侵袭转移能力不同的卵巢癌细胞株HO8910和HO-8910PM中的表达,并进行统计学分析.结果 基因芯片筛选显示,42种miRNA在SKOV-3ip和SKOV-3细胞株表达差异明显.进一步分析显示,let-7a、let-7e、let-7f、miR-22和miR-886-5p等5种miRNA可能与卵巢癌的侵袭转移密切相关.real-time RT-PCR结果证实,let-7f和miR-22在两组侵袭转移能力不同的卵巢癌细胞(SKOV-3和SKOV-3ip细胞、HO-8910和HO-8910PM细胞)表达差异有统计学意义(均P＜0.05).结论 let-7f和miR-22在侵袭转移能力强的卵巢癌细胞中低表达,可能具有抑癌基因的作用.     

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-449在肿瘤中的作用及其调控机制

超过50％的微小RNA (miRNA)定位于肿瘤相关的基因组扩增区域或脆性位点,可具有癌基因或抑癌基因的功能.近年来研究显示,在人类胃癌、肺癌、卵巢癌等恶性肿瘤中miR-449表达降低,被认为是一个抑癌miRNA.miR-449表达异常可能与肿瘤的发生和发展过程密切相关,研究其功能及调控机制,可为肿瘤诊断、治疗和预后判断提供重要线索.     

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.     

非编码RNA在肿瘤微环境中促进卵巢癌发生发展的研究进展

卵巢癌是严重威胁女性生命健康的恶性肿瘤,治疗效果不佳,预后差。卵巢癌的发病是一个复杂过程,具有多因素、多层次的特点,是目前的研究热点。卵巢癌中各种失调的非编码RNA(ncRNA)可在其独特的肿瘤微环境中调控卵巢癌的发生发展,与卵巢癌的发病机制密切相关。ncRNA如长链非编码RNA(lncRNA)、微小RNA(miRNA)、环状RNA等通过调控靶基因的表达及下游通路,参与卵巢癌细胞的多种生命活动,影响其增殖、凋亡、侵袭转移及耐药过程等,促进卵巢癌的发生发展。本文总结了近年来ncRNA在肿瘤微环境中促进卵巢癌发生发展的研究进展,期望为卵巢癌的诊治寻找新靶点,提供新思路和理论依据。     

微小RNA与肿瘤

近年来微小RNA(miRNA)逐渐成为肿瘤研究的热点.越来越多的研究表明,miRNA已涉及到肿瘤的发生和发展,miRNA的表达与肿瘤的病理进程具有相关性,大约有数百个miRNA在肿瘤中异常表达,miRNA在不同肿瘤中具有时空特异性的表达谱.     

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。     

MicroRNA‐135a‐3p as a promising biomarker and nucleic acid therapeutic agent for ovarian cancer

Ovarian cancer is the most lethal gynecologic malignancy. Recently, several molecularly targeted anticancer agents have been developed for ovarian cancer; however, its prognosis remains extremely poor. The development of molecularly targeted therapy, as well as companion diagnostics, is required to improve outcomes for patients with ovarian cancer. In this study, to identify microRNAs (miRNAs) involved in the progression of ovarian cancer we analyzed serum miRNAs in patients with ovarian cancer using miRNA array and quantitative RT‐PCR and examined the anticancer properties of miRNA expression in ovarian cancer cells. In patients with ovarian cancer, high amount of miR‐135a‐3p in serum samples was significantly associated with favorable clinical prognosis. The amount of miR‐135a‐3p was significantly decreased in patients with ovarian cancer compared with patients with ovarian cysts or normal ovaries. In SKOV‐3 and ES‐2 human ovarian cancer cells, enhanced expression of miR‐135a‐3p induced drug sensitivity to cisplatin and paclitaxel and suppressed cell proliferation and xenograft tumor growth. These findings suggest that miR‐135a‐3p may be considered as a biomarker and a therapeutic agent in ovarian cancer.     

MicroRNA signatures in human ovarian cancer

Epithelial ovarian cancer (EOC) is the sixth most common cancer in women worldwide and, despite advances in detection and therapies, it still represents the most lethal gynecologic malignancy in the industrialized countries. Unfortunately, still relatively little is known about the molecular events that lead to the development of this highly aggressive disease. The relatively recent discovery of microRNAs (miRNA), a class of small noncoding RNAs targeting multiple mRNAs and triggering translation repression and/or RNA degradation, has revealed the existence of a new level of gene expression regulation. Multiple studies involving various types of human cancers proved that miRNAs have a causal role in tumorigenesis. Here we show that, in comparison to normal ovary, miRNAs are aberrantly expressed in human ovarian cancer. The overall miRNA expression could clearly separate normal versus cancer tissues. The most significantly overexpressed miRNAs were miR-200a, miR-141, miR-200c, and miR-200b, whereas miR-199a, miR-140, miR-145, and miR-125b1 were among the most down-modulated miRNAs. We could also identify miRNAs whose expression was correlated with specific ovarian cancer biopathologic features, such as histotype, lymphovascular and organ invasion, and involvement of ovarian surface. Moreover, the levels of miR-21, miR-203, and miR-205, up-modulated in ovarian carcinomas compared with normal tissues, were significantly increased after 5-aza-2'-deoxycytidine demethylating treatment of OVCAR3 cells, suggesting that the DNA hypomethylation could be the mechanism responsible for their overexpression. Our results indicate that miRNAs might play a role in the pathogenesis of human EOC and identify altered miRNA gene methylation as a possible epigenetic mechanism involved in their aberrant expression.     

卵巢癌血清相关miRNAs的筛选及其临床意义

背景与目的：卵巢癌预后较差,发现时通常是晚期,需找寻与卵巢癌发生、发展相关的诊治方法。该研究检测miRNA在上皮性卵巢癌患者术前外周血清及良性卵巢肿瘤患者外周血清中表达情况的差异,筛选差异有统计学意义的miRNA并分析其与上皮性卵巢癌患者临床病理特征、预后等的关系。方法：定制研究相关的48种miRNA表达谱芯片,通过TaqMan低密度微阵列芯片,筛选出有统计学意义的miRNA。采用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)法验证筛选的miRNA在卵巢良、恶性肿瘤患者血清中的表达情况,选择具有统计学意义的miRNA行大样本验证并分析其与肿瘤分期、组织病理及预后等的关系。结果：通过TaqMan低密度微阵列芯片筛选和RTFQ-PCR验证,发现miR-125b在上皮性卵巢癌患者血清中的表达高于良性肿瘤患者(P=0.039),miR-125b在早期患者中的表达量高于晚期患者(P=0.003),术后无残余肿瘤患者表达量高于术后有残余肿瘤患者(P=0.013)。血清miR-125b高表达有利于卵巢癌患者无进展生存期(progression-free survival,PFS)延长(P=0.003),但对总生存期(overall survival,OS)无明显影响(P=0.069)。结论：miR-125b在上皮性卵巢癌的发生、发展中起着关键作用,与患者预后相关,是预测卵巢癌复发的潜在基因,但在肿瘤不同期别的表达情况发生变化,在早期作用比较明显,在晚期或肿瘤残余较多的患者表达较不明显,其作用机制有待进一步研究。     

Identification of Genes and MicroRNAs Involved in Ovarian Carcinogenesis

MicroRNAs (miRNAs) play roles in the clinic, both as diagnostic and therapeutic tools. The identification ofrelevant microRNAs is critically required for ovarian cancer because of the prevalence of late diagnosis and poortreatment options currently. To identify miRNAs involved in the development or progression of ovarian cancer,we analyzed gene expression profiles downloaded from Gene Expression Omnibus. Comparison of expressionpatterns between carcinomas and the corresponding normal ovarian tissues enabled us to identify 508 genesthat were commonly up-regulated and 1331 genes that were down-regulated in the cancer specimens. Functionannotation of these genes showed that most of the up-regulated genes were related to cell cycling, and most ofthe down-regulated genes were associated with the immune response. When these differentially expressed geneswere mapped to MiRTarBase, we obtained a total of 18 key miRNAs which may play important regulatory rolesin ovarian cancer. Investigation of these genes and microRNAs should help to disclose the molecular mechanismsof ovarian carcinogenesis and facilitate development of new approaches to therapeutic intervention.     

miRNAs and ovarian cancer: a miRiad of mechanisms to induce cisplatin drug resistance

Ovarian cancer is the most aggressive gynecological cancer. One reason for the low 5-year survival rate of under 40% is that ovarian tumors usually acquire resistance to the platinum-based compounds used to treat them. Resistance to one such compound, cisplatin, can arise via numerous mechanisms that can be categorized as pre-, post-, on- or off-target. Pre-target mechanisms prevent accumulation of cisplatin in the cell, on-target mechanisms allow DNA damage to be repaired more efficiently, post-target mechanisms prevent the damage from inducing apoptosis and off-target mechanisms increase resistance via unrelated compensatory mechanisms. miRNAs are short non-coding RNAs that influence cellular function by repressing gene expression. Here we describe how miRNAs can induce cisplatin resistance in ovarian cancer cells via pre-, post-, on- and off-target mechanisms. A better understanding of how miRNAs feed into the mechanisms of drug resistance will inform the rational design of combination therapies for ovarian cancer.