microRNA 在浆液性卵巢癌中的研究进展

卵巢癌是女性生殖系统最致命的恶性肿瘤,尽管在临床和基础研究中做了很多的努力,但是卵巢癌的整体存活率并无明显的改善。近年来,越来越多的研究表明,microRNA 的异常表达与上皮性卵巢癌的发生发展有着密切联系,很多的 microRNA 被证实可预测卵巢癌的预后和转移,因此 microRNA 可能成为诊断卵巢癌的新的肿瘤标记物,这将会给卵巢癌的诊治开辟新的途径,为卵巢癌患者带来一片曙光。     

卵巢癌与DNA修复功能相关的研究

对４０例卵巢肿瘤患者和１００例健康人的外周血淋巴细胞按经典的非顺序性ＤＮＡ合成法进行ＤＮＡ修复功能测定。其结果表明卵巢癌患者的ＤＮＡ修复功能明显低于健康者，二者间有显著性差异。另外通过实验利用紫外线照射诱导人淋巴细胞的ＤＮＡ非顺序性合成，估价个体ＤＮＡ修复能力，对癌患者进行前瞻性研究，提供了对癌易感个体的检出方法和早期预防的可能性。     

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.     

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.     

基于microRNA调控网络预测卵巢癌多药耐药相关基因

目的:基于microRNA(miRNA)调控网络预测卵巢癌多药耐药相关基因。方法:综合运用文本挖掘、网络构建和预测等生物信息学分析方法,挖掘卵巢癌化疗耐药相关miRNA和miRNA-靶基因数据,并构建miRNA调控网络,利用已知miRNA对卵巢癌多药耐药相关基因进行预测。结果:文本挖掘出11个与卵巢癌化疗耐药相关的miRNA,包括miR-130a、miR-214、let-7i、miR-125b、miR-376c、miR-199a、miR-93、miR-141、miR-130b、miR-193b*和miR-200c。在miRNA靶基因预测数据软件Target Scan中挖掘出47 077个miRNA-靶基因数据,而Pic Tar挖掘出1 675个miRNA-靶基因数据。在miRNA调控网络中,神经素1基因(neuropilins,NRP1)是最重要的Hub-基因。结论:利用已知miRNA构建miRNA调控网络进而预测卵巢癌多药耐药相关基因是一种行之有效的方法。NRP1极有可能在卵巢癌化疗耐药形成中扮演着重要的角色,是卵巢癌潜在的药物治疗靶点。     

基于组学数据分析的非小细胞肺癌亚型特征识别

目的:探索非小细胞肺癌4种亚型在基因组、转录组层次的特征,实现对肿瘤类型的精确分型,获取能够体现非小细胞肺癌亚型的基因组学特征。方法:利用NMF聚类和生存时间分析,对TCGA数据库中的504个非小细胞肺癌样本的拷贝数变异数据和基因表达数据进行分析,对不同疾病亚型的差异表达基因进行富集分析。结果:所有肺癌患者可根据基因变异信息分为4个类别,它们具有不同的基因组特征,其生存时间曲线具有显著差异,同时发现吸烟是肺癌亚型的一个决定因素。结论:通过检测遗传特征和基因表达特征,有助于对非小细胞肺癌患者进行疾病亚型精准判定。     

lncRNA、microRNA在卵巢癌中的研究进展及相互作用关系

人类基因组中大部分为非编码区,转录产生非编码 RNA(ncRNA) 。这些ncRNA可以在表观遗传水平、转录水平及转录后水平调控基因的表达,进而影响肿瘤的发生和发展,是肿瘤诊断、治疗及预后判断的潜在靶标。微小RNA(microRNA ,miRNA) 和长链非编码RNA(long non-coding RNA,lncRNA) 是 ncRNA 的两个重要分类。越来越多的研究表明lncRNA、microRNA 参与生物体的各种生理及病理过程,其中恶性肿瘤的相关研究最多。卵巢癌是妇科常见的恶性肿瘤疾病,早期诊断困难、预后差。MicroRNA和 lncRNA 在卵巢癌的发生发展中的研究进展及相互作用关系近年来引起了人们的关注。本文就这两者在卵巢癌的发生发展过程中的相互作用机制及研究进展作一综述。     

代谢组学在卵巢癌中的应用

代谢组学是近年发展起来的对某一生物或细胞所有低分子代谢产物进行定性和定量分析的新学科.代谢组学是继基因组学、转录组学及蛋白质组学之后生命科学的重要组成之一.卵巢癌的发生发展必然伴随着代谢改变.代谢组学能给卵巢癌代谢水平一个完整的信息,并能给卵巢癌早期诊断及个体化治疗带来广阔前景.     

MiR-100在卵巢癌中的表达及调控作用

目的:探讨微小RNA-100（miR-100）与卵巢癌之间的相关性,以及miR-100调控卵巢癌细胞功能的机制。方法:采用实时荧光定量反转录PCR技术（qRT-PCR）对7例卵巢癌组织样本和细胞株A2780、Skov3进行检测,分析组织和细胞中miR-100的表达差异。通过细胞功能实验分析miR-100调控卵巢癌发生发展的机制。结果:卵巢癌患者组织中miR-100的相对表达水平显著低于正常对照组织（P<0.05）,在两种卵巢癌细胞株中miR-100的相对表达水平也显著低于对照组人永生化卵巢上皮细胞（P<0.05）。细胞功能实验显示,过表达miR-100能显著抑制卵巢癌细胞株的细胞增殖和迁移,促进细胞凋亡。结论:MiR-100在卵巢癌中表达降低,揭示其可能在卵巢癌的发生发展过程中发挥着抑癌基因的功能。     

酶学检查在卵巢癌中的研究进展

卵巢癌（ovarian cancer,OC）是妇科常见的恶性肿瘤,具有独特的的生物学行为,即使病变已达晚期,其肿瘤细胞仍多局限于腹腔内。OC发生或转移时无典型临床表现,确诊时60％～70％已属晚期,死亡率极高,其远期生存率仅30％～40％,早晚期肿瘤的预后差异显著。近年来随着生物化学、免疫学和分子生物学技术的迅速发展,肿瘤标志物在OC诊疗中应用日趋广泛,现就酶学检查在OC研究中的应用概述如下。     

miRNA与卵巢癌的研究进展

 【摘要】　微小RNA（micro-RNA,即miRNA）是长约21～23nt的非编码短链RNA,是基因表达的转录后调节因子,通过与靶miRNA特异的碱基配对,引起靶miRNA降解或翻译抑制。近年研究表明miRNA在肿瘤的发生和发展中起着重要作用。     

Lymphogenic dissemination of ovarian cancer based on autopsy data

A clinicopathological study of 152 autopsied cases of ovarian cancer was carried out. Metastases in lymph nodes ranked third (57.9%), following lesions in the peritoneum (92.1%) and greater omentum (79.6%). Metastases in lymph nodes were found in 88 cases; almost invariably, they were concomitant with implantation and hematogenous metastases. The sites of lymphogenous lesions were most frequently in paraaortal (72.7%), pelvic (47.7%) and mesenteric (27.3%) lymph nodes. No metastases in lymph collectors were detected in nearly half the cases (42.1%) of generalized malignancy. It was shown that lymphogenous dissemination does not necessarily predominate in the clinical picture even at the terminal stage of the disease.     

Clinicopathological and functional significance of XRCC1 expression in ovarian cancer

X‐ray repair cross‐complementing gene 1 (XRCC1) is essential for DNA base excision repair, single strand break repair and nucleotide excision repair. We investigated clinicopathological and functional significance of XRCC1 expression in ovarian cancers. XRCC1 protein expression was evaluated in 195 consecutive human ovarian cancers and correlated with clinicopathological variables and survival outcomes. Functional preclinical studies were conducted in a panel of XRCC1 deficient and proficient Chinese hamster and Human cancer cells for cisplatin chemosensitivity. Clonogenic assay, neutral COMET assay, γH2AX immunocytochemistry and flow cytometric analyses were performed in cells. In ovarian cancer, 48% of the tumors were positive for XRCC1 expression and significantly associated with higher stage (p = 0.006), serous type tumors (p = 0.008), suboptimal de‐bulking (p = 0.004) and platinum resistance (p < 0.0001). Positive XRCC1 had twofold increase of risk of death (p = 0.007) and progression (p < 0.0001). In the multivariate Cox model, XRCC1 expression was independently associated with cancer specific [p = 0.038] and progression free survival [p = 0.003]. Preclinically, XRCC1 negative cells were sensitive to cisplatin compared to XRCC1 positive cells. Sensitivity to cisplatin in XRCC1 negative cells was associated with accumulation of DNA double strand breaks and G2/M cell cycle arrest. XRCC1 expression is associated with adverse clinicopathological and survival outcomes in patients. Preclinical data provides mechanistic functional evidence for cisplatin sensitivity in XRCC1 negative cells. XRCC1 is a promising predictive biomarker in ovarian cancer.     

Screening key microRNAs for castration-resistant prostate cancer based on miRNA/mRNA functional synergistic network

High-throughput methods have been used to explore the mechanisms by which androgen-sensitive prostate cancer (ASPC) develops into castration-resistant prostate cancer (CRPC). However, it is difficult to interpret cryptic results by routine experimental methods. In this study, we performed systematic and integrative analysis to detect key miRNAs that contribute to CRPC development. From three DNA microarray datasets, we retrieved 11 outlier microRNAs (miRNAs) that had expression discrepancies between ASPC and CRPC using a specific algorithm. Two of the miRNAs (miR-125b and miR-124) have previously been shown to be related to CRPC. Seven out of the other nine miRNAs were confirmed by quantitative PCR (Q-PCR) analysis. MiR-210, miR-218, miR-346, miR-197, and miR-149 were found to be over-expressed, while miR-122, miR-145, and let-7b were under-expressed in CRPC cell lines. GO and KEGG pathway analyses revealed that miR-218, miR-197, miR-145, miR-122, and let-7b, along with their target genes, were found to be involved in the PI3K and AKT3 signaling network, which is known to contribute to CRPC development. We then chose five miRNAs to verify the accuracy of the analysis. The target genes of each miRNA were altered significantly upon transfection of specific miRNA mimics in the C4–2 CRPC cell line, which was consistent with our pathway analysis results. Finally, we hypothesized that miR-218, miR-145, miR-197, miR-149, miR-122, and let-7b may contribute to the development of CRPC through the influence of Ras, Rho proteins, and the SCF complex. Further investigation is needed to verify the functions of the identified novel pathways in CRPC development.     

基于数据挖掘分析KIF14与SSK1在卵巢癌组织中的表达及临床意义

目的:应用生物信息学方法挖掘卵巢癌的相关基因,探讨其表达情况及临床意义,为卵巢癌的诊断和靶向治疗提供依据.方法:从GEO(Gene Expression Omnibus)数据库下载基因芯片数据集GSE23391、GSE18520和GSE54388,利用其在线分析工具GEO2R筛选卵巢癌的差异表达基因(DEGs).运用数...     

Identification of suitable endogenous controls for gene and miRNA expression studies in irradiated prostate cancer cells

This study aimed to to evaluate the stability of commonly used endogenous control genes for messenger RNA (mRNA) (N?=?16) and miRNAs (N?=?3) expression studies in prostate cell lines following irradiation. The stability of endogenous control genes expression in irradiated (6 Gy) versus unirradiated controls was quantified using NormFinder and coefficient of variation analyses. HPRT1 and 18S were identified as most and least stable endogenous controls, respectively, for mRNA expression studies in irradiated prostate cells. SNORD48 and miR16 miRNA endogenous controls tested were associated with low coefficient of variations following irradiation (6 Gy). This study highlights that commonly used endogenous controls can be responsive to radiation and validation is required prior to gene/miRNAs expression studies.     

miRNA在卵巢癌早期诊断和预后中作用的研究进展

[摘要] 卵巢癌是女性生殖器官常见的恶性妇科肿瘤之一。由于缺乏有效的生物标志物用于诊断和个性化治疗,超过70％的卵巢癌患者诊断时已是晚期,并且5 年生存率低于30％。因此,迫切需要新的诊断和预后标志物来推进和启动更个性化的治疗,最终提高患者的存活率。miRNA是一类小的非编码RNA,主要通过转录后抑制负调节基因表达。近年来,一些研究表明,miRNA在卵巢癌组织中表达失调,有可能作为卵巢癌的诊断和预后生物标志物。另外,最近的研究显示,miRNA还可以作为化疗敏感性的预测因子和治疗靶点。本文主要从miRNA在卵巢癌组织中的差异表达、miRNA与卵巢癌的诊断和miRNA与卵巢癌的预后3 个方面进行阐述,为推进和启动卵巢癌患者的诊断和个性化治疗提供借鉴。     

Identification of a novel BRCA1 large genomic rearrangement in a Spanish breast/ovarian cancer family

Background Alterations in BRCA1 gene are responsible for the majority of hereditary breast and/or ovarian cancers. However, the frequency of detected germline mutations is lower than expected by linkage analysis. Standard PCR-based screening methods are mainly used for detecting mutations, but the large genomic rearrangements are commonly overlooked. The purpose of this study was to confirm and characterize a novel deletion identified in BRCA1 gene which has not yet been reported to date. Methods Multiplex ligation-dependent probe amplification was used to analyze BRCA1 rearrangements in 255 unrelated index patients with familial breast and/or ovarian cancer negative for BRCA1/BRCA2 mutations studied in Program of Genetic Counselling on Cancer of Valencia Community (Spain). The breakpoints of detected novel rearrangement were characterized by sequencing. Results and discussion Five different rearrangements in the BRCA1 gene were identified in five unrelated index patients out of the 225 (2%). We found four large genomic rearrangements already described consisting in a 1A/1B and 2 deletion; deletion of exons 5–7; deletion of exons 8–13; exon 20 deletion. Additionally, we found the novel g.8097_22733del14637 deletion that encompasses exons 3–5. This deletion affects the RING domain of the BRCA1 protein and it is suggestive of having a negative impact on its function. Conclusion The new mutation here reported broadens the mutational spectrum of large rearrangements. Furthermore, the five large rearrangements found in patients non-carriers of BRCA1/BRCA2 mutations reinforce the need of studying BRCA1 large genomic rearrangements in genetic counselling programs.