miR-130a靶向调节SMAD4基因对卵巢癌SKOV3细胞增殖和侵袭的影响

目的探讨miR-130a对卵巢癌SKOV3细胞增殖及侵袭能力的影响。方法将卵巢癌SKOV3细胞分为miR-130a抑制剂组、miR-130a模拟物组和对照组,分别将miR-130a抑制剂或miR-130a模拟物转染至miR-130a抑制剂组或miR-130a模拟物组细胞,对照组细胞转染无关序列,Real-time PCR法检测各组细胞miR-130a表达水平,分别用MTT方法与Transwell细胞侵袭实验检测转染后各组SKOV3细胞的增殖与侵袭能力变化。Real-time PCR与Western blot实验分别检测各组细胞SMAD4 mRNA和蛋白表达水平。结果转染miR-130a模拟物后,SKOV3细胞miR-130a的表达水平显著升高,SKOV3细胞的增殖与侵袭能力显著降低,SMAD4 mRNA及蛋白的表达水平显著降低(P0.01);转染miR-130a抑制剂后,SKOV3细胞miR-130a的表达水平显著降低,SKOV3细胞的增殖与侵袭能力显著升高,SMAD4 mRNA及蛋白的表达水平显著升高(P0.01)。结论 miR-130a抑制卵巢癌SKOV3细胞的增殖和侵袭可能与下调SMAD4的表达相关。     

miR-26a靶向调节GSK-3β基因对卵巢癌SKOV3细胞增殖和侵袭的影响

目的探讨miR-26a对卵巢癌SKOV3细胞增殖及侵袭能力的影响。方法将卵巢癌SKOV3细胞分为miR-26a抑制剂组、miR-26a模拟物组和对照组,分别将miR-26a抑制剂或miR-26a模拟物转染至miR-26a抑制剂组或miR-26a模拟物组细胞,对照组细胞转染无关序列,Real-time PCR法检测各组细胞miR-26a表达水平,分别用MTT方法与Transwell细胞侵袭实验检测转染后各组SKOV3细胞的增殖与侵袭能力变化。Real-time PCR与Western blot实验分别检测各组细胞GSK-3βm RNA和蛋白表达水平。结果与对照组相比,miR-26a抑制剂组SKOV3细胞miR-26a表达水平显著降低,miR-26a模拟物组则显著升高(P0.01)。与对照组相比,miR-26a抑制剂组SKOV3细胞增殖与侵袭能力显著降低,GSK-3βm RNA及蛋白表达水平显著升高,miR-26a模拟物组SKOV3细胞增殖与侵袭能力显著升高,GSK-3βm RNA及蛋白表达水平显著降低(P0.01)。结论 miR-26a促进卵巢癌SKOV3细胞的增殖和侵袭可能与下调GSK-3β的表达相关。     

microRNA138对卵巢癌细胞增殖的影响

目的研究microRNA 138在卵巢癌患者中的表达,探讨microRNA 138对卵巢癌SKOV3细胞增殖的影响。方法收集卵巢癌患者标本38例,同时收集相应的癌旁组织19例。利用荧光定量PCR方法检测各个组织中microRNA 138的表达水平。用脂质体作为载体将microRNA 138模拟物转染至SKOV3细胞,CCK-8方法检测细胞增殖能力的变化。结果 microRNA 138在卵巢癌组织中的表达水平明显低于癌旁组织,P0.01。过表达microRNA 138能够显著抑制SKOV3细胞的增殖。结论 microRNA 138表达上调能够抑制卵巢癌细SKOV3增殖,其可能参与卵巢癌的发生发展过程。     

miR-101靶向调节c-Fos基因对卵巢癌SKOV3细胞增殖和侵袭的影响

目的探讨miR-101对卵巢癌SKOV3细胞增殖及侵袭能力的影响。方法将卵巢癌SKOV3细胞分为miR-101抑制剂组、miR-101模拟物组和对照组,分别将miR-101抑制剂或miR-101模拟物转染至miR-101抑制剂组或miR-101模拟物组细胞,对照组细胞转染无关序列,Real-time PCR法检测各组细胞miR-101表达水平,分别用MTT方法与Transwell细胞侵袭实验检测转染后各组SKOV3细胞的增殖与侵袭能力变化。Real-time PCR与Western blot实验分别检测各组细胞c-Fos mRNA和蛋白表达水平。结果转染miR-101模拟物后,SKOV3细胞miR-101的表达水平显著升高,SKOV3细胞的增殖与侵袭能力显著降低,c-Fos mRNA及蛋白的表达水平显著降低(P0.01);转染miR-101抑制剂后,SKOV3细胞miR-101的表达水平显著降低,SKOV3细胞的增殖与侵袭能力显著升高,c-Fos mRNA及蛋白的表达水平显著升高(P0.01)。结论 miR-101抑制卵巢癌SKOV3细胞的增殖和侵袭可能与下调c-Fos的表达相关。     

miR-132 靶向调控Ezrin 抑制卵巢癌细胞增殖、促进凋亡的实验研究

目的:探讨微小核糖核酸分子(miRNA)-132 在卵巢癌中生物学作用和作用靶点。方法:收集22 例卵巢癌及癌旁非肿瘤组织标本,RT-PCR 检测miR-132 表达量;RT-PCR 检测人正常卵巢上皮细胞和卵巢癌细胞系中miR-132 表达量;选择miR-132 表达量最高或最低的卵巢癌细胞株,分别转染阴性对照质粒(NC)和miR-132 mimic 质粒,RT-PCR 检测转染后miR-132 表达量;CCK-8 法检测细胞增殖,流式细胞仪检测细胞凋亡,Western blot 检测Ezrin 蛋白表达。结果:卵巢癌组织中miR-132 表达量显著低于癌旁非肿瘤组织,而卵巢癌细胞系中miR-132 表达量显著低于正常卵巢上皮细胞,差异均有统计学意义(P<0.05);选择卵巢癌细胞株中miR-132 表达量最低卵巢癌SKOV3 细胞株进行基因转染,与转染阴性对照质粒相比,转染miR-132 mimic 质粒后miR-132 表达量显著上升,细胞增殖显著降低,细胞凋亡显著增加,差异均有统计学意义(P<0.05);Western blot 结果显示,上调miR-132 表达后,卵巢癌SKOV3 细胞株中Ezrin 蛋白表达显著上升(P<0.05)。结论:在卵巢癌中,miR-132 可能作为一种抑癌基因通过靶向调控Ezrin 抑制卵巢癌细胞增殖、促进凋亡。     

circAGFG1/miR-487a-3p轴调控卵巢癌SKOV3细胞增殖、迁移、侵袭及EMT的实验研究

目的 探讨circAGFG1对卵巢癌SKOV3细胞增殖、迁移、侵袭及上皮间质转化（EMT）的影响和作用机制。方法 RT-qPCR检测31例卵巢癌患者的癌组织和对应的癌旁组织中circAGFG1和miR-487a-3p表达。体外培养SKOV3细胞,分别转染circAGFG1小干扰RNA、miR-487a-3p模拟物或抑制剂后,CCK-8法检测细胞增殖,Transwell法对细胞迁移和侵袭进行检测,Western blot对细胞中Ki-67、MMP-2、MMP-9、Vimentin和E-cadherin蛋白表达进行检测。双荧光素酶报告基因实验验证circAGFG1和miR-487a-3p调控关系。结果 circAGFG1在卵巢癌组织中表达升高,miR-487a-3p表达降低。下调circAGFG1或上调miR-487a-3p阻碍SKOV3细胞增殖、迁移、侵袭及EMT。circAGFG1在SKOV3细胞中靶向负调控miR-487a-3p表达。敲减miR-487a-3p逆转下调circAGFG1对SKOV3细胞增殖、迁移、侵袭及EMT的影响。结论 下调circAGFG1可能通过靶向上调miR-...     

过表达miR-17-5p对卵巢癌SKOV3细胞增殖的影响及可能机制

目的探讨miR-17-5p对卵巢癌SKOV3细胞增殖的影响及可能机制。方法将卵巢癌SKOV3细胞分为miR-17-5p模拟物组、miR-17-5p阴性对照组及空白对照组,将miR-17-5p模拟物转染至miR-17-5p模拟物组细胞,阴性对照组细胞转染无关序列,空白对照组细胞不作任何处理,采用real time PCR方法验证其转染效率,用MTT方法检测转染后各组SKOV3细胞的增殖能力变化。采用双荧光素酶报告基因验证P21是否为miR-17-5p的靶基因,real-time PCR与Western blot实验分别检测各组细胞P21m RNA和蛋白表达水平。结果与对照组相比,miR-17-5p模拟物组SKOV3细胞miR-17-5p表达水平显著升高,但细胞增殖能力显著降低。双荧光素酶报告基因分析结果显示,P21为miR-17-5p的靶基因;过表达miR-17-5p后,P21m RNA及蛋白表达水平显著降低(P0.01)。结论 miR-17-5p抑制卵巢癌SKOV3细胞的增殖可能与下调P21的表达相关。     

HOTAIR通过靶向抑制miR-519d促进人卵巢癌SKOV3细胞增殖

目的研究HOTAIR对人卵巢癌SKOV3细胞增殖的影响以及可能机制。方法使用Lipofectamine TM2000试剂将HOTAIR过表达慢病毒载体以及HOTAIR沉默慢病毒载体分别稳定转染SKOV3卵巢癌细胞后,应用Realtime PCR验证其转染效率;应用CCK-8法检测HOTAIR对人卵巢癌SKOV3细胞增殖的影响;应用Real-time PCR检测人SKOV3卵巢癌细胞中miR-519dm RNA表达变化。应用双荧光素酶报告基因验证HOTAIR和miR-519d存在靶向结合并明确其结合位点。结果和对照组相比,HOTAIR过表达显著促进了人卵巢癌SKOV3细胞的增殖,极大降低了miR-519d在SKOV3细胞中的m RNA水平;HOTAIR和miR-519d存在靶向结合,并明确了其结合位点;miR-519d过表达显著抑制了人卵巢癌SKOV3细胞增殖能力;miR-519d过表达有效阻断了HOTAIR促进SKOV3细胞增殖的作用。结论 HOTAIR能够通过靶向抑制miR-519d,提高人卵巢癌SKOV3细胞的增殖能力。     

卵巢癌组织中miR-574-5p的表达及其下调后对SKOV-3细胞增殖与侵袭的影响

目的观察miR-574-5p在卵巢组织中的表达及下调miR-574-5p表达对卵巢癌细胞株SKOV-3增殖与侵袭的影响。方法实时PCR检测41例卵巢癌组织及对应癌旁正常卵巢组织miR-574-5p的表达;随机将SKOV-3细胞分为空白对照组、阴性对照组和miR-574-5p抑制物组,分别用MTT方法与Transwell细胞侵袭实验检测各组SKOV3细胞的增殖与侵袭能力变化。结果卵巢癌组织中miR-574-5p相对表达量为1.29±0.18,显著高于癌旁正常卵巢组织的0.51±0.07(P0.01);转染miR-574-5p抑制物后,SKOV3细胞的增殖能力明显下降,穿膜能力亦明显减弱(P0.01)。结论卵巢癌组织中miR-574-5p的表达水平异常增高,抑制miR-574-5p的表达能够降低SKOV3细胞的增殖与侵袭。     

miR-19a介导JAK/STAT信号通路促进卵巢癌细胞增殖的研究

目的 探讨miR-19a对卵巢癌细胞增殖的影响及可能机制.方法 选取人卵巢癌细胞株SKOV3、正常人卵巢表面上皮细胞HOSEpiC以及30例上皮卵巢癌组织和20例癌旁组织为研究对象.对SKOV3细胞株进行转染,分为NC组(未进行任何处理)、miR-NC组(转染miR-NC)、miR-19a组(转染miR-19a mimic).MTT检测细胞增殖能力;克隆形成实验检测细胞生长;流式细胞术检测细胞周期;采用实时荧光定量PCR检测卵巢癌中miR-19a、JAK2、STAT3、p-JAK2和p-STAT3基因mRNA水平;Western blot检测细胞JAK2、STAT3、p-JAK2、p-STAT3蛋白表达水平.结果 卵巢癌组织miR-19a水平高于正常卵巢组织,SKOV3细胞株中miR-19a表达水平高于HOSEpiC细胞(P<0.01).转染后48 h和72 h,与NC组、miR-NC组相比,miR-19a组细胞增殖能力明显升高(P<0.05).与NC组、miR-NC组相比,miR-19a组细胞克隆数目、S期细胞百分比明显升高(P<0.05).与NC组、miR-NC组相比,miR-19a组细胞p-JAK2、p-STAT3蛋白表达水平,p-JAK2/JAK2、p-STAT3/STAT3比值明显升高(P<0.05).与NC组、miR-NC组相比,miR-19a组细胞p-JAK2、p-STAT3基因mRNA表达水平,p-JAK2/JAK2、p-STAT3/STAT3比值明显升高(P<0.05).结论 卵巢癌组织miR-19a高表达,miR-19a过表达可能通过Akt/mTOR通路促进卵巢癌细胞的增殖.     

同型半胱氨酸与卵巢癌研究进展

同型半胱氨酸是体内代谢过程中的一种氨基酸产物,在许多疾病患者的血液中其均有所升高。卵巢癌是女性生殖系统常见的肿瘤之一,尽管其发病率低于宫颈癌和子宫体癌位居第三,但死亡率却高居首位。研究发现同型半胱氨酸可作为许多恶性肿瘤的肿瘤标志物,本文通过对既往文献的回顾,进一步对同型半胱氨酸与卵巢癌的关系进行总结。     

TP53 and ovarian cancer

Ovarian cancer represents the fourth most frequent type of cancer among females and is the leading cause of death from gynecological cancer in the western world. This review describes gene alterations in ovarian cancer. Specific emphasis is placed on genetic alterations and the prevalence of TP53 (p53) gene alterations in the distinct biological ovarian tumors (benign, borderline, and malignant) and histological subtypes (serous, mucinous, endometrioid, clear cell), as well as in BRCA1-associated hereditary ovarian cancer. Although multi-modality treatment regimens, including cytoreductive surgery and cisplatin-containing combination chemotherapy, have usefully prolonged survival, the overall cure rate of the disease has not changed dramatically. Ovarian cancer is difficult to eradicate completely by surgery and many patients have only a partial response to postoperative chemotherapy and/or many will develop chemotherapy resistance. All these important factors contribute to the poor prognosis of ovarian cancer patients. In this review, the putative prognostic or predictive value of TP53 in ovarian cancer is addressed.     

溶血磷脂酸与卵巢肿瘤

溶血磷脂酸是一种具有细胞间信号传导作用的脂类小分子物质，具有广泛的生物学效应。研究发现卵巢癌患者的腹水中存在溶血磷脂酸，它可以促进癌细胞的生长；卵巢癌患者的血浆中具有明显高于正常对照组的溶血磷脂酸，用于卵巢癌的诊断具有较高的敏感性及特异性。优于Ca125。卵巢癌的细胞呆分泌溶血磷脂酸，且细胞中存在溶血磷脂酸的自分泌环，它与肿瘤的发展，耐药及预后密切相关。这将对卵巢癌的治疗提供新的可能。     

Prognosis of ovarian cancer

Fifty-three patients were treated in the gynaecological unit of the Mater Hospital for ovarian cancer between 1980-86. The demographic features of the patients reviewed were similar to those of the Southern Tumour Registry (1981-85), and in the absence of a national tumour registry are presumed to be representative of the country as a whole. Data from the STR indicates that the annual incidence of ovarian cancer is 20/100,000; extrapolating from these figures to the national would suggest that approximately 280 women develop ovarian cancer each year. The majority of Mater patients (72%) had either stage I or stage II ovarian cancer which is at variance with other studies and may reflect an under-staging at initial laparotomy. Their survival rates were better than those of the STR, probably because they had presented earlier and had a lower portion of undifferented tumours. Ovarian cancer is the main cause of death from genital cancer in Ireland. While the stage of disease at diagnosis is critical to survival, chemotherapy did not influence survival.     

The Anti-Mullerian hormone and ovarian cancer

The Anti-Mullerian hormone (AMH), which is produced by fetal Sertoli cells, is responsible for regression of Mullerian ducts, the anlagen for uterus and Fallopian tubes, during male sex differentiation. Ovarian granulosa cells also secrete AMH from late in fetal life. The patterns of expression of AMH and its type II receptor in the post-natal ovary indicate that AMH may play an important role in ovarian folliculogenesis. Recent advances in the physiological role of AMH has stimulated interest in the significance of AMH as a diagnostic marker and therapeutic agent for ovarian cancer. Currently, AMH has been shown to be a circulating marker specifically for granulosa cell tumour (GCT). Its diagnostic performance seems to be very good, with a sensitivity ranging between 76 and 93%. In patients treated for GCT, AMH may be used post-operatively as marker for the efficacy of surgery and for disease recurrence. Based on the physiological inhibitory role of AMH in the Mullerian ducts, it has been proposed that AMH may inhibit epithelial ovarian cancer cell both in vitro and in vivo. These observations will be the basis for future research aiming to investigate the possible clinical role of AMH as neo-adjuvant, or most probably adjuvant, therapy for ovarian cancer.     

Managing hereditary ovarian cancer

In this review we present an overview of recent developments in the management of hereditary ovarian cancer. Until recently, intensive screening of the ovaries was recommended to mutation carriers and their first-degree female relatives. However, since screening is not effective in detecting early-stage ovarian cancer, women are counselled for a prophylactic bilateral salpingo-oophorectomy (pBSO) shortly after child-bearing age (>35 years). Many mutation carriers already choose to undergo pBSO to reduce their cancer risks; however, the age of prophylactic surgery may interfere with reproductive and other important (psychosexual) issues in life. Due to the protective effect of oral contraceptives regarding ovarian cancer, we advise women at increased risk of ovarian cancer to use oral contraceptive pills for 3–5 years early in life (<25 years of age), when the absolute incidence of breast cancer is extremely low. A transient increased relative risk of breast cancer due to oral contraceptives at this age will result in a negligible increased absolute number of breast cancers, while the risk reduction of ovarian cancer remains for life. Research should aim at finding new molecular markers and screening strategies for detecting early-stage ovarian cancer in women with a hereditary ovarian cancer trait.     

肿瘤干细胞与卵巢癌

卵巢肿瘤干细胞（OCSCs)是存在于卵巢癌组织中的一类具有自我更新和多向分化潜能的细胞,表面共表达CD44和CD117分子标记。虽然其起源不是很确定,但目前倾向于认为卵巢表面上皮细胞来源于OCSCs。研究OCSCs自我更新机制和表观遗传学的改变,可为肿瘤发生的机制及新药的开发提供很好的基础