长链非编码RNA在子痫前期胎盘中的差异表达研究

目的:研究子痫前期(PE)胎盘长链非编码RNA(LncRNAs)的差异表达情况。方法:选取妊娠20周以后诊断为子痫前期的孕妇作为研究组(n=20),同期足月(≥37周)采用剖宫产终止妊娠的孕妇作为对照组(n=24)。采用基因芯片技术分析两组胎盘的LncRNAs的差异表达情况,通过q-PCR技术对筛选的LncRNAs进行验证。结果:与正常对照组相比,PE组胎盘差异表达的LncRNAs共174条,其中107条LncRNAs表达上调,67条LncRNAs表达下调。q-PCR验证结果显示,LncRNAs(ENST00000593000和NR002161)在PE胎盘组织中的表达显著高于正常妊娠胎盘组织(P0.05),ENST00000593000升高3.24倍,NR002161升高2.67倍,且均定位于Y染色体。女婴胎盘组织中均不表达ENST00000593000和NR002161。结论:PE组胎盘LncRNAs表达存在显著改变,Y染色体上LncRNAs的改变是男婴PE发生可能危险因素。     

卵巢癌中相关长链非编码RNA的研究进展

卵巢癌是女性生殖系统第二常见的恶性肿瘤,其发生发展涉及多种遗传学和环境因素,其生存率低及易复发性已成为研究的重点和难点.基因组计划近年的研究显示,在基因组序列中仅有不到2％的核酸序列可用于编码蛋白质,其余98％以上的序列不编码任何蛋白质,这些基因序列一度被认为是无功能序列,但是近年来的研究却表明这些无功能序列蕴含着...     

卵巢癌中相关长链非编码RNA的研究进展

卵巢癌是女性生殖系统第二常见的恶性肿瘤,其发生发展涉及多种遗传学和环境因素,其生存率低及易复发性已成为研究的重点和难点。基因组计划近年的研究显示,在基因组序列中仅有不到2%的核酸序列可用于编码蛋白质,其余98%以上的序列不编码任何蛋白质,这些基因序列一度被认为是"无功能序列",但是近年来的研究却表明这些无功能序列蕴含着丰富的信息和功能。这些"无功能序列"中大多数为长度超过200个碱基的长链非编码RNA(lncRNA)。LncRNA是由哺乳动物基因组编码的长度超过200 bp的一组内源性细胞RNA,近年来学者们己经发现了许多与恶性肿瘤有关的lncRNA,并认为它们可能在调控肿瘤发生、发展及侵袭过程中发挥作用。本文概述了lncRNA在卵巢癌中的研究进展。     

长链非编码RNA与妇科肿瘤研究进展

长链非编码RNA(long non-coding RNA,lnc RNA)是一类长度超过200个碱基的RNA分子。由于不参与编码形成蛋白质分子,早期观点普遍认为lnc RNA分子是基因组转录过程中形成的副产物,被定义为不具备生物学功能的转录组"背景噪音"。然而,近年来越来越多的研究发现,在哺乳动物基因组中,lnc RNA分子首先由数千个基因位点转录形成,随后,经过加工的成熟lnc RNA分子在动物胚胎发育、基因表达调节以及疾病发生和发展中起关键性调控作用。目前已有研究证实,在多种人类肿瘤疾病中,部分特异性lnc RNA分子的表达水平在疾病进展的各时期中发生显著了变化。在妇科恶性肿瘤中lnc RNA分子表达变化以及lnc RNA通过上下游靶向分子对疾病发生和发展的影响也有了许多报道。综述这一领域最新的研究进展。     

长链非编码RNA HOTAIR在妇科恶性肿瘤中的研究进展

长链非编码RNA(LncRNA)主要以RNA形式在表观遗传学水平、转录水平及转录后水平等多个层面调控基因表达进而调控机体的多种生物学过程。同源异型盒基因转录反义基因间RNA(Linc-HOTAIR)是lncRNAs的重要一分子,调控基因表达过程主要为通过染色体重塑、促进蛋白质泛素化及充当竞争性内源RNA(ceRNA)调节miRNA等方式,是目前研究的一大热点。本文结合HOTAIR在肿瘤中相关研究的最新报道,将其在妇科常见恶性肿瘤中的进展予以综述。     

上皮性卵巢癌相关的长链非编码RNA的研究进展

机体内大约70%的RNA不编码蛋白质,其中长度超过200个核苷酸的一类被称为长链非编码RNA(long non-coding RNA,lncRNA)。lncRNA虽然不编码蛋白质,但具有复杂的调控基因表达的功能。lncRNA的表达具有时间特异性、组织特异性和疾病特异性的特点,近年来在肿瘤发生发展中的作用日趋受到重视,被看作是有潜力的肿瘤标记物以及治疗靶点。上皮性卵巢癌是最常见的卵巢癌,目前尚缺乏敏感的早期筛查指标和有效治疗方案,且病死率仍位居妇科恶性肿瘤首位。关于lncRNA在上皮性卵巢癌组织和细胞系中表达量变化、功能以及作用机制的研究方兴未艾,并成为研究热点。总结目前发现的lncRNA对上皮性卵巢癌发生、发展的影响以及lncRNA发挥作用的相关机制,有助于进一步了解上皮性卵巢癌发病机制,发掘更加敏感的肿瘤标记物以及更加有效的治疗靶点。     

长链非编码RNA与子宫内膜癌关系的研究进展

子宫内膜癌是妇科常见的恶性肿瘤之一,其发病率逐年增长。长链非编码RNA(lncRNA)是非编码RNA家族的成员之一,近年研究发现其在子宫内膜癌的病理过程中发挥重要的调控作用,成为研究热点。lncRNA可作为促进基因,通过人类第10号染色体上磷酸酶和张力蛋白同源缺失的基因/磷脂酰肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PTEN/PI3K/AKT/mTOR)、Wnt/β连环蛋白(Wnt/β-Catenin)、细胞外信号调节激酶/腺苷酸活化蛋白激酶(ERK/AMPK)等多种信号通路调控子宫内膜癌细胞的增殖、迁移、侵袭、凋亡过程,亦可通过PTEN/PI3K/AKT/mTOR途径抑制子宫内膜癌过程。在lncRNA调控子宫内膜癌的过程中,形成的lncRNA-miRNA轴可作为未来干预治疗的新方向。lncRNA还可影响化疗药的耐药性,并对子宫内膜癌的诊断和预后有重要价值。综述近年lncRNA和子宫内膜癌的研究,为lncRNA对于子宫内膜癌的诊断、预后或治疗靶点提供理论依据。     

长链非编码RNA与妊娠关系的研究现状

长链非编码RNAs(lnc RNAs)是一类转录本长度超过200nt、非编码蛋白质的RNAs。lnc RNAs能控制调节细胞的增殖、分化、凋亡及干细胞多能性。研究表明,lnc RNAs参与机体多种生命活动的调节,早期胚胎发育及病理性妊娠结局也受到lnc RNAs的一过性或长时间的调控。lnc RNAs差异表达与复发性流产、子痫前期、早产及胎儿生长受限等病理性妊娠结局密切相关。     

长链非编码RNA在妇科肿瘤中的作用机制及研究进展

长链非编码RNA(lncRNA)是近年来肿瘤领域的研究热点,其数量众多,种类多样,功能多变,已被发现在机体多种病理生理过程中发挥重要的调控作用,且其功能失调与肿瘤的发生发展密切相关。目前已发现的lncRNA仅仅只是冰山一角,人们对lncRNA的研究尚在起步阶段,诸多功能和作用机制尚不明确。本文现综述lncRNA在卵巢癌、宫颈癌及子宫内膜癌等妇科常见恶性肿瘤中的作用机制和研究新进展。     

长链非编码RNA HOTAIR在宫颈癌中的研究进展

宫颈癌是我国最常见的女性生殖系统肿瘤之一,严重威胁女性的生命健康。 HOX 转录反义RNA（HOTAIR）是一种典型的反义长链非编码RNA,在宫颈癌细胞中的表达显著升高,与宫颈癌的发生发展密切相关。近年HOTAIR在宫颈癌发生发展中发挥作用的机制研究发现其抑制大量抑癌基因的表达,广泛参与宫颈癌细胞的增殖、凋亡、侵袭和迁移等各个环节,通过调节放疗耐受、抗逆转录和免疫靶向助力晚期宫颈癌治疗,在宫颈癌的遗传易感性中起着重要的作用,且与肿瘤进展及不良预后有显著相关性。未来根据HOTAIR的分子机制设计治疗靶点,通过大样本、多中心、前瞻性的临床试验证实其有效性和实用性,将为宫颈癌患者的早期诊断和个性化治疗提供新的思路。     

miRNA和lncRNA及相关信号转导通路对滋养细胞浸润功能的影响及其机制

微小RNA（miRNA）是一种内源性表达的小分子非编码RNA,通过转录后抑制调控约30%的基因表达,很多研究表明miRNA在调控滋养细胞复制、迁移、浸润等功能中发挥重要作用。长链非编码RNA（lncRNA）是长度大于200个核苷酸的非编码RNA,通过表观遗传效应、细胞周期调控和细胞分化调控等影响滋养细胞复制、迁移、浸润等。细胞内信号通路的正常传导保证滋养细胞浸润功能正常而不会如肿瘤细胞一样无限制地生长和侵袭。不同的RNA或不同的信号通路所作用的靶点不同,最终引起滋养细胞浸润功能改变的过程也不相同。综述近年非编码RNA及其相关信号转导通路对滋养细胞浸润功能所产生的影响及机制。     

Preeclampsia: Diagnosis and management of the atypical presentation

Preeclampsia, eclampsia, and HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome remain as major obstetric problems that plague a large percentage of women resulting in an equally large percentage of maternal and perinatal morbidities. It is important that a clinician makes the most accurate diagnosis possible to prevent these adverse maternal and perinatal outcomes. In general, most women will have a classical presentation of preeclampsia (hypertension and proteinuria) at >20 weeks gestation and <48 hours postpartum. However, recent studies have suggested that some women will develop preeclampsia without the classical findings. The purpose of this review is to increase awareness of the non-classical and atypical features of preeclampsia, eclampsia, and HELLP syndrome and their respective management. Atypical cases are those that develop before 20 weeks, beyond 48 hours postpartum and those that present with some of the signs and symptoms of preeclampsia without the usual hypertension or proteinuria. By formulating a rational stepwise approach towards diagnosis, we may prevent the costly consequence of a missed diagnosis and its eventual possible fatalities.     

Down-regulated long non-coding RNA-ATB in preeclampsia and its effect on suppressing migration,proliferation, and tube formation of trophoblast cells

Preeclampsia is a pregnancy-specific syndrome and is one of the main causes of maternal, fetal, and neonatal morbidity and mortality. Inadequate trophoblast invasion and failure of uterine spiral artery remodeling exert a major role in the development of preeclampsia, especially the early-onset one. LncRNA-ATB is verified to be aberrantly expressed in many cancers and promote the invasion-metastasis and proliferation cascades. But little is known of lncRNA-ATB's role in preeclampsia. The aim of current study is to identify the changes of lncRNA-ATB in preeclampsia and its effects on trophoblast. The lncRNA-ATB levels were decreased in placental samples collected from preeclampsia women (n = 51) compared to those of healthy pregnant women (n = 40) by qRT-PCR analysis. Besides, it is demonstrated that lncRNA-ATB was intense stained in the trophoblast of the placenta by performing in-situ hybridization. By designing RNA interference species to suppress lncRNA-ATB and specific plasmids designed to overexpress lncRNA-ATB, we identify the role of lncRNA-ATB on the functions of trophoblast cell-line, HTR-8/SVneo. Inhibition of endogenous lncRNA-ATB decreased migration, proliferation, tube-formation of HTR-8/SVneo cells. In addition, overexpression of lncRNA-ATB promoted migration, proliferation, and tube-formation of HTR-8/SVneo cells. Therefore, lncRNA-ATB might be involved in the pathogenesis of preeclampsia by regulating the process of trophoblast invasion and endovascular formation.     

Preeclampsia recurrence and prevention

Women with a previous pregnancy complicated by preeclampsia have an increased risk for recurrence in subsequent pregnancies. For severe preeclamptic women in an initial pregnancy, recurrence rates for any type of preeclampsia are very high, approaching 50% in some studies. Significant maternal and fetal complications are more common in recurrent preeclampsia compared with an initial episode. For women who have experienced a pregnancy complicated by preeclampsia, a systematic evaluation for underlying risk factors may identify a specific pathway suitable for a specific intervention. Although some progress has been made in developing potential therapeutic options to prevent preeclampsia recurrence, there is a great need for better data to determine who will benefit most from any specific therapy.     

The Administration of Antithrombin III in the Management of Severe Preeclampsia

In severe preeclampsia/eclampsia a disseminated intravascular coagulation (DIC)-like syndrome is a prominent feature. Low levels of antithrombin III (AT-III; heparin cofactor) have been described in this syndrome. The objective of this pilot study is to determine whether the low levels of AT-III can be increased to normal by the intravenous administration of purified, concentrated, human AT-III. All patients entered into the study manifested thrombocytopenia, hemolytic anemia, coagulopathy, evidence of liver disease, and/or a bleeding diathesis. Each patient received a dose of AT-III equivalent to the amount in 3,000 ml of plasma. The levels of AT-III as measured by a functional assay were significantly increased (1.5–2x) following the initial 3,000 unit bolus of AT-III and prior to any other blood replacement therapy. The response of individual patients is proportional to the initial level of AT-III. In the control group there was no difference between the predelivery levels of AT-III and those obtained 12–24 hr postpartum. Therefore, the intravenous administration of AT-III may be useful in the treatment of patients with severe preeclampsia or eclampsia.     

错误折叠蛋白与子痫前期相关研究进展

子痫前期(pre-eclampsia,PE)是一种全身性异质性妊娠期并发症,具体发病机制尚不明确,目前仍缺乏准确可靠的预测、诊断及有效的治疗方法.已知错误折叠蛋白是内质网氧化应激的产物,且错误折叠蛋白与许多人类疾病的发生、发展相关.近年来,有学者发现在PE孕妇的胎盘、血液及尿液中存在错误折叠蛋白,而且PE患者体内的错误...     

长链非编码RNA及其在妇科肿瘤发生发展中的作用

长链非编码RNA(long non-coding RNA,lnc RNA)曾被认为是基因组转录过程中的"噪音"而被科学界忽视。然而,近年来的许多研究表明lnc RNA并非是"垃圾",而是具有功能的RNA分子,故而受到广泛重视。相比于短链非编码RNA,lnc RNA可谓是"后起之秀",相关研究刚崭露头角,但就目前已有的研究表明,lnc RNA在基因表达调控方面发挥着十分重要的作用,在临床疾病尤其是肿瘤的诊治方面有着不可估量的科学价值。综述lnc RNA的功能、作用机制及其在妇科相关肿瘤发生发展中的意义。     

Influence of ethnicity on the clinical and biologic expression of pre-eclampsia in the ECLAXIR study

Objective

To determine whether ethnic origin is related to the clinical and biologic expression of pre-eclampsia.

Methods

In a secondary analysis of information collected in the ECLAXIR study in France between May 2003 and October 2006, the data from 284 white European, 84 Maghrebian and 158 African women were evaluated in a case–control study of the genetic and endothelial determinants of pre-eclampsia.

Results

African origin was a risk factor for pre-eclampsia before 28 weeks of gestation. Symptoms related to hypertension, such as neurologic signs and changes in biologic parameters (e.g. hemolysis elevated liver enzymes, low platelet count [HELLP] syndrome), occurred more frequently among white European women. After logistic regression, gestational age at delivery was lower for African women than for white European women (33.4 weeks versus 34.4 weeks of gestation, P = 0.04).

Conclusion

The results suggest that ethnic origin may have a role in the expression of pre-eclampsia, and should therefore be taken into account in prenatal surveillance. Further research on the genetic factors involved in endothelial dysfunction is warranted.     

血管损伤因子与子痫前期发病机制的研究

子痫前期是妊娠妇女和围生儿死亡的主要原因之一,迄今病因仍未明了。目前研究认为,内皮细胞损伤、血管生成抑制和血管间炎症在其发病中起重要作用。一些胎盘及血管源性循环因子的释放,包括血管内皮生长因子、可溶性血管内皮生长因子-1、血管紧张素Ⅱ受体1的自身抗体及肿瘤坏死因子-α、白细胞介素1(IL-1)和IL-6、正五聚蛋白3等通过不同途径引起母体血管内皮广泛损伤及全身性炎症反应;血管舒缩因子失衡,例如一氧化氮(NO)、前列环素及肾上腺髓质素等血管舒张因子表达减少,而内皮素、血管紧张素Ⅱ等血管收缩因子表达增加也可导致血管功能紊乱。其中某些标记物还可作为子痫前期发病的预测指标。