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Pivotal role of long non-coding ribonucleic acid-X-inactive specific transcript in regulating immune checkpoint programmed death ligand 1 through a shared pathway between miR-194-5p and miR-155-5p in hepatocellular carcinoma 认领 引用 被引量:10
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作者 Sara M Atwa Heba Handoussa +2 位作者 Karim M Hosny Margarete Odenthal Hend M El Tayebi 《World Journal of Hepatology》 2020年第12期1211-1227,共17页
BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight.However,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatoria... BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight.However,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatorial therapy with immune checkpoint blockade.Non-coding ribonucleic acid(ncRNA)driven regulation is a major mechanism of epigenetic modulation.Given the wide range of ncRNAs that co-opt in programmed cell-death protein 1(PD-1)/programmed death ligand 1(PD-L1)regulation,and based on the literature,we hypothesized that miR-155-5p,miR-194-5p and long non-coding RNAs(lncRNAs)X-inactive specific transcript(XIST)and MALAT-1 are involved in a regulatory upstream pathway for PD-1/PD-L1.Recently,nutraceutical therapeutics in cancers have received increasing attention.Thus,it is interesting to study the impact of oleuropein on the respective study key players.AIM To explore potential upstream regulatory ncRNAs for the immune checkpoint PD-1/PD-L1.METHODS Bioinformatics tools including microrna.org and lnCeDB software were adopted to detect targeting of miR-155-5p,miR-194-5p and lncRNAs XIST and MALAT-1 to PD-L1 mRNA,respectively.In addition,Diana tool was used to predict targeting of both aforementioned miRNAs to lncRNAs XIST and MALAT-1.HCC and normal tissue samples were collected for scanning of PD-L1,XIST and MALAT-1 expression.To study the interaction among miR-155-5p,miR-194-5p,lncRNAs XIST and MALAT-1,as well as PD-L1 mRNA,a series of transfections of the Huh-7 cell line was carried out.RESULTS Bioinformatics software predicted that miR-155-5p and miR-194-5p can target PDL1,MALAT-1 and XIST.MALAT-1 and XIST were predicted to target PD-L1 mRNA.PD-L1 and XIST were significantly upregulated in 23 HCC biopsies compared to healthy controls;however,MALAT-1 was barely detected.MiR-194 induced expression elevated the expression of PD-L1,XIST and MALAT-1.However,overexpression of miR-155-5p induced the upregulation of PD-L1 and XIST,while it had a negative impact on MALAT-1 expression.Knockdown of XIST did have an impact on PD-L1 expression;however,following knockdown of the negative regulator of X-inactive specific transcript(TSIX),PD-L1 expression was elevated,and abolished MALAT-1 activity.Upon co-transfection of miR-194-5p with siMALAT-1,PD-L1 expression was elevated.Co-transfection of miR-194-5p with siXIST did not have an impact on PD-L1 expression.Upon co-transfection of miR-194 with siTSIX,PD-L1 expression was upregulated.Interestingly,the same PD-L1 expression pattern was observed following miR-155-5p cotransfections.Oleuropein treatment of Huh-7 cells reduced the expression profile of PD-L1,XIST,and miR-155-5p,upregulated the expression of miR-194-5p and had no significant impact on the MALAT-1 expression profile.CONCLUSION This study reported a novel finding revealing that opposing acting miRNAs in HCC,have the same impact on PD-1/PD-L1 immune checkpoint by sharing a common signaling pathway. 展开更多
关键词 Hepatocellular carcinoma X-inactive specific transcript MiR-155-5p MiR-194-5p Programmed cell-death protein 1/Programmed death ligand 1 Immune checkpoint
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Long noncoding RNA X-inactive specific transcript regulates NLR family pyrin domain containing 3/caspase-1-mediated pyroptosis in diabetic nephropathy 认领 引用 被引量:11
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作者 Jia Xu Qin Wang +4 位作者 Yi-Fan Song Xiao-Hui Xu He Zhu Pei-Dan Chen Ye-Ping Ren 《World Journal of Diabetes》 SCIE 2022年第4期358-375,共18页
BACKGROUND NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology.Long noncoding RNAs(lncRNAs)are active participators of diabetic nephropathy(DN).X inactive specific transcript(X... BACKGROUND NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology.Long noncoding RNAs(lncRNAs)are active participators of diabetic nephropathy(DN).X inactive specific transcript(XIST)expression has been reported to be elevated in the serum of DN patients.AIM To evaluate the mechanism of lncRNA XIST in renal tubular epithelial cell(RTEC)pyroptosis in DN.METHODS A DN rat model was established through streptozotocin injection,and XIST was knocked down by tail vein injection of the lentivirus LV sh-XIST.Renal metabolic and biochemical indices were detected,and pathological changes in the renal tissue were assessed.The expression of indicators related to inflammation and pyroptosis was also detected.High glucose(HG)was used to treat HK2 cells,and cell viability and lactate dehydrogenase(LDH)activity were detected after silencing XIST.The subcellular localization and downstream mechanism of XIST were investigated.Finally,a rescue experiment was carried out to verify that XIST regulates NLR family pyrin domain containing 3(NLRP3)/caspase-1-mediated RTEC pyroptosis through the microRNA-15-5p(miR-15b-5p)/Toll-like receptor 4(TLR4)axis.RESULTS XIST was highly expressed in the DN models.XIST silencing improved renal metabolism and biochemical indices and mitigated renal injury.The expression of inflammation and pyroptosis indicators was significantly increased in DN rats and HG-treated HK2 cells;cell viability was decreased and LDH activity was increased after HGtreatment. Silencing XIST inhibited RTEC pyroptosis by inhibiting NLRP3/caspase-1. Mechanistically,XIST sponged miR-15b-5p to regulate TLR4. Silencing XIST inhibited TLR4 by promotingmiR-15b-5p. miR-15b-5p inhibition or TLR4 overexpression averted the inhibitory effect ofsilencing XIST on HG-induced RTEC pyroptosis.CONCLUSIONSilencing XIST inhibits TLR4 by upregulating miR-15b-5p and ultimately inhibits renal injury inDN by inhibiting NLRP3/caspase-1-mediated RTEC pyroptosis. 展开更多
关键词 Diabetic nephropathy Pyroptosis Renal tubular epithelial cell Long noncoding RNA X-inactive specific transcript microRNA-15b-5p Toll-like receptor 4 NLR family pyrin domain containing 3/caspase-1 pathway
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lncRNA XIST调控miR-17-5p/FOSL1轴对胆囊癌细胞增殖、迁移和侵袭的影响 认领 引用
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作者 陈李康 姚磊 彭莹莹 《肝胆胰外科杂志》 CAS 2026年第2期115-123,共9页
目的探讨长链非编码RNA(lncRNA)X染色体失活特异性转录本(XIST)调控微小RNA-17-5p(miR-17-5p)/FOS样抗原1(FOSL1)轴对胆囊癌(GBC)细胞增殖、迁移和侵袭的影响。方法qRT-PCR法检测GBC组织和细胞株中mRNA表达;双荧光素酶报告基因实验验证l... 目的探讨长链非编码RNA(lncRNA)X染色体失活特异性转录本(XIST)调控微小RNA-17-5p(miR-17-5p)/FOS样抗原1(FOSL1)轴对胆囊癌(GBC)细胞增殖、迁移和侵袭的影响。方法qRT-PCR法检测GBC组织和细胞株中mRNA表达;双荧光素酶报告基因实验验证lncRNA XIST与miR-17-5p,miR-17-5p与FOSL1的互作;将EH-GB1细胞分为Ctrl组、sh-NC组、sh-XIST组、sh-XIST+inhibitor-NC组、sh-XIST+inhibitor-miR-17-5p组、mimic-NC组、mimic-miR-17-5p组、mimic-miR-17-5p+OE-NC组、mimic-miR-17-5p+OE-FOSL1组。台盼蓝染色和平板克隆实验检测EH-GB1细胞增殖;划痕试验检测EH-GB1细胞迁移;Transwell实验检测EH-GB1细胞侵袭;Western blotting检测EH-GB1细胞中Ki67、Cyclin D1、MMP-2、CD44、FOSL1蛋白的表达。裸鼠移植瘤实验检测敲低lncRNA XIST对GBC肿瘤生长的影响。结果GBC组织和细胞中miR-17-5p呈低表达,lncRNA XIST、FOSL1呈高表达。sh-XIST组细胞存活率、增殖数、划痕愈合率、侵袭数,Ki67、Cyclin D1、MMP-2、CD44表达水平低于sh-NC组、Ctrl组(P<0.05);sh-XIST+inhibitor-miR-17-5p组细胞存活率、增殖数、划痕愈合率、侵袭数及Ki67、Cyclin D1、MMP-2、CD44表达水平高于sh-XIST组、sh-XIST+inhibitor-NC组(P<0.05)。mimic-miR-17-5p组细胞存活率、增殖数、划痕愈合率、侵袭数及Ki67、Cyclin D1、MMP-2、CD44、FOSL1表达水平低于mimic-NC组、Ctrl组(P<0.05);mimic-miR-17-5p+OE-FOSL1组细胞存活率、增殖数、划痕愈合率、侵袭数及Ki67、Cyclin D1、MMP-2、CD44、FOSL1表达水平高于mimic-miR-17-5p组、mimic-miR-17-5p+OE-NC组(P<0.05)。lncRNA XIST可以靶向负调控miR-17-5p,而miR-17-5p可以靶向负调控FOSL1(P<0.05)。XIST敲低组裸鼠移植瘤体积、体质量,肿瘤FOSL1蛋白、lncRNA XIST表达水平低于阴性对照组,miR-17-5p表达水平高于阴性对照组(P<0.05)。结论lncRNA XIST通过调控miR-17-5p/FOSL1轴促进GBC细胞的增殖、迁移和侵袭。 展开更多
关键词 长链非编码RNA X染色体失活特异性转录本 微小RNA-17-5p FOS样抗原1 胆囊癌 增殖 迁移 侵袭
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Xist lncRNA介导X染色体失活及应用研究进展 认领 引用 被引量:4
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作者 陶维昆 刘波 +2 位作者 黄飞 王杰 高庆华 《中国畜牧兽医》 CAS 北大核心 2022年第1期216-223,共8页
在哺乳动物胚胎发育过程中,雌性胚胎细胞中一条X染色体转录沉默,导致两性间的剂量补偿称为X染色体失活(X chromosome inactivation,XCI)。X染色体失活中心(X chromosome inactivation center,XIC)是XCI的主要调控区域,X-非活性特异性转... 在哺乳动物胚胎发育过程中,雌性胚胎细胞中一条X染色体转录沉默,导致两性间的剂量补偿称为X染色体失活(X chromosome inactivation,XCI)。X染色体失活中心(X chromosome inactivation center,XIC)是XCI的主要调控区域,X-非活性特异性转录物(X-inactive specific transcript,Xist)位于该区域中且是XCI的关键部分。Xist长链非编码RNA(long chain non-coding RNA,lncRNA)是一种非活性的特异性转录物,能够招募如RNA互作结合蛋白(RNA interaction binding protein,RBP)、染色质修饰因子等一系列辅助因子,促使染色体和细胞核空间结构、染色质组成及X连锁基因转录水平发生改变,从而将有活性的染色体转化为无活性的染色体。对小鼠、人及其他物种研究显示,XCI普遍存在于哺乳动物胚胎发育中,是胚胎存活的基础,然而不同物种胚胎中却存在一些特异性差异。此外,癌症、肿瘤等一些人类疾病也与XCI有关。目前关于XCI机制研究比较零散,作者就Xist lncRNA介导XCI的主要分子机理、调控机制及在不同物种中的研究进行概述。 展开更多
关键词 哺乳动物 X染色体失活(XCI) X染色体失活中心(XIC) X-非活性特异性转录物(Xist) lncRNA
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血清lncRNA-XIST、lncRNA-MALAT1水平与多囊卵巢综合征不孕症患者胰岛素抵抗及促排卵治疗后妊娠结局的关联性研究 认领 引用 被引量:3
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作者 雷金梅 冯玉环 +2 位作者 张鸥 高商 陈薇 《中国临床新医学》 2024年第8期901-906,共6页
目的探讨lncRNA-XIST、lncRNA-MALAT1与多囊卵巢综合征(PCOS)不孕症患者胰岛素抵抗及促排卵治疗后妊娠结局的关联性。方法招募2020年2月至2022年1月于唐山市妇幼保健院进行促排卵治疗的125例PCOS不孕症患者(PCOS不孕症组),另选取同期体... 目的探讨lncRNA-XIST、lncRNA-MALAT1与多囊卵巢综合征(PCOS)不孕症患者胰岛素抵抗及促排卵治疗后妊娠结局的关联性。方法招募2020年2月至2022年1月于唐山市妇幼保健院进行促排卵治疗的125例PCOS不孕症患者(PCOS不孕症组),另选取同期体检健康的女性125名作为对照组。比较两组血清lncRNA-XIST、lncRNA-MALAT1水平及稳态模型评估的胰岛素抵抗指数(HOMA-IR)。采用Pearson相关分析探讨血清lncRNA-XIST、lncRNA-MALAT1水平与HOMA-IR的相关性。采用多因素logistic回归分析探讨影响PCOS不孕症患者促排卵治疗后妊娠结局的因素。结果与对照组比较,PCOS不孕症组血清lncRNA-XIST水平及HOMA-IR较高,lncRNA-MALAT1水平较低,差异有统计学意义(P<0.05)。HOMA-IR与血清lncRNA-XIST水平呈正相关(r=0.689,P<0.001),与血清lncRNA-MALAT1水平呈负相关(r=-0.771,P<0.001)。PCOS不孕症患者经促排卵治疗后累积临床妊娠率为43.20%(54/125)。多因素logistic回归分析结果显示,较高的促黄体生成素(LH)/卵泡刺激素(FSH)比值[OR(95%CI)=1.121(1.005~1.278)]和血清lncRNA-XIST水平[OR(95%CI)=1.252(1.014~1.449)]是促进PCOS不孕症患者治疗后未妊娠的独立危险因素(P<0.05),较高的血清抗米勒管激素(AMH)水平[OR(95%CI)=0.518(0.348~0.771)]、lncRNA-MALAT1水平[OR(95%CI)=0.394(0.238~0.652)]是促进PCOS不孕症患者治疗后获得妊娠的保护因素(P<0.05)。结论PCOS不孕症患者血清lncRNA-XIST呈高表达,lncRNA-MALAT1呈低表达,且两个指标水平与胰岛素抵抗、促排卵治疗后妊娠结局密切相关。 展开更多
关键词 多囊卵巢综合征 不孕症 胰岛素抵抗 妊娠结局 lncRNA-XIST lncRNA-MALAT1
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血清lncRNAXIST和SIRT1水平与DR的关系及其诊断价值 认领 引用 被引量:2
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作者 文晓霞 郭红建 汤云霞 《国际眼科杂志》 CAS 2024年第8期1218-1222,共5页
目的:检测2型糖尿病(T2DM)患者血清长链非编码RNA(lncRNA)X非活性特异性转录本(XIST)、沉默信息调节因子2相关酶1(SIRT1)表达水平,并探讨其与糖尿病视网膜病变(DR)的相关性及其诊断价值。方法:前瞻性研究。选取2022-01/2023-02在我院收... 目的:检测2型糖尿病(T2DM)患者血清长链非编码RNA(lncRNA)X非活性特异性转录本(XIST)、沉默信息调节因子2相关酶1(SIRT1)表达水平,并探讨其与糖尿病视网膜病变(DR)的相关性及其诊断价值。方法:前瞻性研究。选取2022-01/2023-02在我院收治T2DM患者214例作为研究对象。根据是否发生视网膜病变,分为非DR组126例126眼,DR组88例88眼。另选取同期体检健康者130例为对照组。检测三组血清lncRNA XIST、SIRT1水平并进行比较。采用Pearson法分析lncRNA XIST和SIRT1表达与DR的关系,受试者工作特征(ROC)曲线评价血清lncRNA XIST、SIRT1单独及联合对DR的预测价值,多因素Logistic回归分析影响T2DM患者发生DR的因素。结果:与对照组比较,非DR组和DR组血清lncRNA XIST、SIRT1水平依次降低(均P<0.05);DR患者血清lncRNA XIST和SIRT1水平呈正相关(r=0.639,P<0.05);ROC分析显示,血清lncRNA XIST、SIRT1联合预测DR的曲线下面积(AUC)为0.940,高于血清lncRNA XIST、SIRT1单独检测的AUC(0.855、0.875)。Logistic回归分析显示,lncRNA XIST(OR=0.752)、SIRT1(OR=0.694)是DR发生的影响因素(均P<0.01)。结论:DR患者血清lncRNA XIST、SIRT1水平均降低,lncRNA XIST联合SIRT1对DR发生有较好的评估效能。 展开更多
关键词 长链非编码RNA(lncRNA)X非活性特异性转录本(XIST) 沉默信息调节因子2相关酶1(SIRT1) 2型糖尿病(T2DM) 糖尿病视网膜病变(DR) 诊断价值
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lncRNA XIST靶向miR-15b-5p调控细胞凋亡及自噬参与帕金森病发病机制研究 认领 引用 被引量:8
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作者 李岩 《徐州医科大学学报》 CAS 2020年第7期476-481,共6页
目的探讨长链非编码RNA(lncRNA)X染色体失活特异转录本(XIST)对帕金森病(PD)的潜在分子机制。方法用1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导建立PD模型。用爬杆和转棒法检测小鼠行为变化。四甲基偶氮唑盐法和流式细胞术检测人神经母... 目的探讨长链非编码RNA(lncRNA)X染色体失活特异转录本(XIST)对帕金森病(PD)的潜在分子机制。方法用1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导建立PD模型。用爬杆和转棒法检测小鼠行为变化。四甲基偶氮唑盐法和流式细胞术检测人神经母细胞瘤细胞(SH-SY5Y细胞)活力和凋亡。双荧光素酶报告基因法、实时荧光定量聚合酶链反应(qRT-PCR)、Western blot、免疫组化探讨lncRNA XIST在PD中的分子机制。结果PD体内外模型XIST表达上调,miR-15b-5p表达下调。沉默XIST(si-XIST)可缩短小鼠准备向下爬行的时间,延长停留时间。此外,si-XIST也可增加酪氨酸羟化酶阳性(TH+)神经元数。miR-15b-5p是XIST的靶基因。结论si-XIST可通过调控miR-15b-5p抑制PD的自噬和凋亡。 展开更多
关键词 帕金森病 长链非编码RNA X染色体失活特异转录本 miR-15b-5p 凋亡 自噬
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Factors affecting early embryonic development in cattle:relevance for bovine cloning 认领 引用 被引量:2
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作者 Yanna DANG Kun ZHANG 《Frontiers of Agricultural Science and Engineering》 2019年第1期33-41,共9页
Female infertility represents a major challenge for improving the production ef?ciency in the dairy industry. Historically, fertility has declined whereas milk yield has increased tremendously due to intensive genetic... Female infertility represents a major challenge for improving the production ef?ciency in the dairy industry. Historically, fertility has declined whereas milk yield has increased tremendously due to intensive genetic selection. In vivo evidence reveals about 60% pregnancy loss takes place during the ?rst month following fertilization. Meanwhile, early embryo development is signi?cant for somatic cell nuclear transfer in cattle as a large proportion of cloned embryos fail to develop beyond periimplantation stage. Oocyte quality is of utmost importance for the early embryo to develop to term for both fertilized and cloned embryos. Epigenetic reprogramming is a key process occurring after fertilization and critical roles of epigenetic modi?ers during preimplantation development are now clear. Incomplete epigenetic reprogramming is believed to be a major limitation to cloning ef?ciency.Treatment of cloned embryos with epigenetic modifying drugs(e.g., Trichostatin A) could greatly improve cloning ef?ciency in both mice and cattle. Recently, the rapid progress in high-throughput sequencing technologies has enabled detailed deciphering of the molecular mechanisms underlying these events. The robust ef?ciency of genomic editing tools also presents an alternative approach to the functional annotation of genes critical to early development. 展开更多
关键词 bovine cloning embryo development somatic cell nuclear transfer X-inactive specific transcript
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