This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief and authors. Following the publication of the above article, the Editor was notified by a concerned reader that the authors supplied duplicated images. Specifically, that in Fig. 5 A, both FACS panels are identical and in Fig 5E, two different proteins (HK2 and PDK1) have the same western blot. After checking the data in relation with Fig. 5A and E, the authors have confirmed that the two pictures indeed have the problems of duplication. The authors reported that this problem came from the authors' unintentional behavior, which may be due to a copy and paste error in the manner of image processing. The authors sincerely apologize for the inconvenience caused to our Editors and readers. Due to this duplication error, the authors and Editor have made the decision to retract this paper.

The long noncoding RNA (lncRNA) DLGAP1-AS2 has recently been characterized as an oncogenic lncRNA in several cancers. However, its biological roles and clinical significance in gastric cancer (GC) remains barely understood. In this study, we performed a systematic analysis of DLGAP1-AS2 expression with data from the TCGA and GEO database as well as our clinic GC samples. In agreement with previous studies, our findings demonstrated that DLGAP1-AS2 was significantly up-regulated in GC and its high expression was associated with poor prognosis, suggesting that DLGAP1-AS2 might be a putative oncogenic lncRNA of GC. Loss of DLGAP1-AS2 restricted cell proliferation, migration, and invasion in GC cell lines. Mechanically, Wnt1 was identified as the downstream target of DLGAP1-AS2 by using bioinformatics analysis coupled with qPCR and Western blot assays. Furthermore, DLGAP1-AS2 was found to directly interact with the transcriptional repressor Six3, and this interaction hampered Six3 binding to the promoter regions of the Wnt1 gene, thereby leading to transcriptional activation of Wnt1. Consequently, GC cells lacking DLGAP1-AS2 showed a decreased Wnt1 expression and weakened Wnt/β-catenin signaling. Further, Six3 silencing could reverse the above effects, highlighting a pivotal role of Six3 in the DLGAP1-AS2-mediated activation of Wnt/β-catenin signaling. Either genetic (Wnt1 knockdown) or pharmacological (LF3) inhibition of Wnt/β-catenin signaling could effectively abolish the activation of Wnt/β-catenin signaling by Six3 depletion, thereby preventing GC cell malignant transformation. Taken together, our results suggest that DLGAP1-AS2 functions as an oncogenic factor by directly interacting with Six3 to relieve its suppression on Wnt1 expression, thereby driving the malignancy of GC. DLGAP1-AS2/Six3/Wnt1/β-catenin signaling axis might serve as a promising diagnostic and therapeutic target for GC.

目的:研究长链非编码RNA(long non-coding RNA,lncRNA)SPATA3-AS1在胃癌患者癌组织和血浆中的表达及临床意义,并进一步探讨其对胃癌细胞株的影响及其潜在机制.方法:采用实时荧光定量PCR(qRT-PCR)检测80例胃癌及癌旁组织、29例胃癌患者和29例健康者血浆中SPATA3-AS1的表达水平;对胃癌患者SPATA3-AS1表达与其临床病理特征行统计学分析.敲减SPATA3-AS1,分别转染胃癌AGS、HGC-27细胞,采用细胞增殖、克隆形成、Transwell实验及流式细胞术分别检测细胞增殖、迁移、侵袭和凋亡;采用qRT-PCR检测肿瘤相关基因mRNA的表达水平.结果:SPATA3-AS1在胃癌组织中呈高表达,其表达与淋巴结转移、肿瘤TNM分期、肿瘤浸润深度及肿瘤预后相关;胃癌患者血浆中SPATA3-AS1也呈高表达,其表达与淋巴结转移、肿瘤直径、肿瘤TNM分期呈正相关.血浆中SPATA3-AS1表达水平诊断胃癌ROC曲线下面积为0.788.敲减SPATA3-AS1后,胃癌AGS、HGC-27细胞增殖及移动活力减弱,细胞凋亡能力增强.同时N-钙黏蛋白、Twist1、Snail mRNA表达下调而E-钙黏蛋白mRNA表达上调.结论:SPATA3-AS1在胃癌患者癌组织及血浆中呈高表达并与其预后相关;敲减SPATA3-AS1后胃癌细胞增殖、迁移及侵袭等能力均受到抑制,细胞凋亡增强,可能与对上皮间质转化过程的调控有关.

目的 探讨LncRNA NPSR1-AS1在胃癌(gastric cancer,GC)中的表达及临床意义,分析其对胃癌细胞生物学行为的影响和作用机制.方法 收集86例胃癌患者癌组织及癌旁组织,另收集21例胃癌患者及体检健康者血浆标本,采用实时荧光定量PCR(RT-qPCR)检测各组LncRNA NPSR1-AS1的表达水平,并与患者临床病理资料进行相关性分析.siRNA敲减NPSR1-AS1后,采用细胞增殖试验、Transwell试验、流式细胞术检测癌细胞增殖、迁移、侵袭、凋亡能力,并用RT-qPCR检测肿瘤相关基因表达量的变化.结果 LncRNA NPSR1-AS1在胃癌组织中的表达水平显著升高,且与肿瘤大小(t=11.02,P<0.01)、淋巴结转移(t=2.30,P<0.05)、TNM分期(t=3.55,P<0.01)、肿瘤血管或神经侵袭(t=3.10,P<0.05)显著相关;血浆LncRNA NPSR1-AS1筛查胃癌的ROC曲线下面积(AUCROC)为0.696.LncRNA NPSR1-AS1敲减后可使GSK-3β(t=16.15,P<0.01)和E-cadherin(t=10.17,P<0.01)表达上调,β-catenin(t=4.869,P<0.05)、N-cadherin(t=3.77,P<0.05)、Snail(t=9.372,P<0.01)和MMP2(t=15.57,P<0.01)表达下调.结论 LncRNA NPSR1-AS1敲减可抑制胃癌细胞增殖、迁移及侵袭并诱导其凋亡,其作用机制与上皮-间质转化(EMT)有关.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief and authors. Following the publication of the above article, the Editor was notified by a concerned reader that the authors supplied duplicated images. Specifically, that in Fig. 5A, both FACS panels are identical and in Fig. 5E, two different proteins (HK2 and PDK1) have the same western blot. After checking the data in relation with Fig. 5A and Fig. 5E, the authors have confirmed that the two pictures indeed have the problems of duplication. The authors reported that this problem came from the authors’ unintentional behavior, which may be due to a copy and paste error in the manner of image processing. The authors sincerely apologize for the inconvenience caused to our Editors and readers. Due to this duplication error, the authors and Editor have made the decision to retract this paper.

NLRP3炎症小体是先天免疫系统的重要组成部分,能够介导caspase-1激活,促进前炎症因子白介素(interleukin,IL)-1β/IL-18的释放.NLRP3炎症小体的异常激活已被证明与多种疾病有关,包括帕金森、动脉粥样硬化、急性肺损伤等疾病.非编码RNA(non-coding RNA,ncRNA)如微小RNA(microR-NA,miRNA)和长链非编码RNA(long non-coding RNA,lncRNA)是指不能编码蛋白质的RNA分子,能够在转录或转录后水平调控NLRP3的表达,并在NLRP3炎症小体异常激活的相关疾病中发挥重要作用.本文就相关领域的最新进展展开综述,以期为进一步治疗NLRP3炎性小体相关疾病提供新的思路.

目的 探讨长链非编码RNA(long non-coding RNA,lncRNA)KCNMB2-AS1在胃癌(gastric cancer,GC)组织和血浆中的表达水平、临床意义及其对胃癌细胞生物学功能的影响和可能机制.方法 实时荧光定量PCR(QRT-PCR)检测82例配对胃癌及癌旁对照组织、31例患者和31例健康体检者血浆KCNMB2-AS1的表达;分析KCNMB2-AS1表达量与临床病理特征的相关性.通过细胞计数、克隆形成、Transwell实验及流式细胞术观察敲减KCNMB2-AS1后胃癌细胞增殖、迁移、侵袭和凋亡的变化.QRT-PCR检测敲减KCNMB2-AS1对肿瘤相关基因表达水平的影响.结果 KCNMB2-AS1在胃癌组织和血浆中显著高表达,其表达水平与肿瘤大小、淋巴结转移、TNM分期及预后密切相关.血浆KCNMB2-AS1表达水平诊断胃癌的ROC曲线下面积为0.865.敲减KCNMB2-AS1抑制胃癌细胞增殖、迁移和侵袭并诱导其凋亡,间质标志N-cadherin、Fibronectin 1和转录因子Twist1、Slug、ZEB1表达下调.结论 KCNMB2-AS1在胃癌组织及血浆中均高表达,其高表达与疾病进展及不良预后相关.血浆KCNMB2-AS1表达水平对诊断胃癌具有一定价值.敲减KCNMB2-AS1抑制胃癌细胞增殖、迁移和侵袭,诱导胃癌细胞凋亡并抑制EMT过程.

Activation of nucleotide-binding domain leucine-rich repeat containing family pyrin domain containing 3 (NLRP3) inflammasome in Kupffer cells (KCs) contributes significantly to hepatic ischemia/reperfusion (I/R) injury, while the mechanism of how NLRP3 inflammasome is regulated remains less well defined. Recent evidence has showed that mitophagy acts as a central player for maintaining mitochondrial homeostatis through elimination of damaged mitochondria, leading to the prevention of hyperinflammation triggered by NLRP3 activation. In this study, we aimed at investigating the potential role of PTEN-induced kinase 1 (PINK1)mediated mitophagy in hepatic I/R injury. C57BL/6 mice subjected to partial warm hepatic I/R or primary KCs exposed to anoxia/reoxygenation (A/R) was used as in vivo or in vitro model, respectively. Mitophagy was measured by protein levels of PINK1, Parkin, LC3B-II, TOMM20 and p62. NLRP3, caspase-1 and IL-1 beta at mRNA and/or protein levels were used as indicators of inflammasome activation. Our results demonstrated remarkable hepatic inflammation and NLRP3 inflammasome activation during hepatic I/R, along with increased PINK1mediated mitophagy. Notably, overexpression of PINK1 in vivo attenuated hepatic I/R injury, ROS production, NLRP3 activation and hepatic inflammation. In parallel, A/R challenge in vitro also triggered NLRP3 activation in KCs accompanied by increase in mitophagy. Enhanced mitophagy mediated by PINK1 overexpression further inhibited NLRP3 activation and reversed the KC-mediated inflammatory injury to hepatocytes. Kinase-dead mutation of PINK1 completely abolished the above protective effects by PINK1. Blocking of mitophagy/autophagy by silencing of PINK1/Parkin, ATG5, NDP52 or OPTN showed the totally opposite effects, respectively. Treatment with different autophagic inhibitors also consistently reversed the PINK1-mediated effects, suggesting that an intact PINK1-mediated mitophagy signaling was crucial for ablation of NLRP3 signaling in the presence of A/R. Together, these results support a critical role of PINK1-mediated mitophagy in mitochondrial quality control for KC activation and function in hepatic I/R.

目的:探讨长链非编码RNA (long non-coding RNA,lncRNA) DLGAP1-AS2在胃癌中的表达及其临床意义.方法:从美国癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库下载胃腺癌相关数据集,分析肿瘤组织与正常组织中DLGAP1-AS2的表达差异.采用实时荧光定量PCR法测定85例胃癌组织及其相应癌旁组织,以及25例胃癌患者和25例健康者血浆中DLGAP1-AS2的表达水平,分析胃癌组织中DLGAP1-AS2表达水平与胃癌患者临床病理特征的相关性.通过转染小干扰RNA的方法敲减胃癌AGS细胞中DLGAP1-AS2的表达后,分别采用活细胞计数法、克隆形成实验及Transwell小室法检测下调DLGAP1-AS2对胃癌AGS细胞增殖、迁移和侵袭能力的影响,并采用蛋白质印迹法检测胃癌AGS细胞中上皮-间质转化(epithelial-mesenchymal transition,EMT)相关基因表达水平的变化.结果:TCGA数据库分析发现,DLGAP1-AS2在胃癌组织中的表达水平明显高于正常胃组织(P＜0.001).实时荧光定量PCR检测证实DLGAP1-AS2在胃癌组织中表达水平明显增高(P＜0.05),并与肿瘤TNM分期、淋巴结转移和患者总生存率明显相关(P值均＜0.05);而且DLGAP1-AS2在胃癌患者血浆中表达水平也明显增高(P＜0.05).敲减DLGAP1-AS2可抑制胃癌AGS细胞增殖、克隆形成、迁移及侵袭(P值均＜0.05),并且明显下调基质金属蛋白酶2 (matrix metalloproteinase 2,MMP2)、Slug、N钙黏蛋白(N-cadherin,N-cad)和Twist蛋白的表达水平(P值均＜0.05).结论:DLGAP1-AS2在胃癌患者癌组织及血浆中表达水平均明显增高.敲减DLGAP1-AS2能抑制胃癌细胞增殖、迁移及侵袭,其作用机制可能与调控EMT相关分子表达有关.

长链非编码RNA(long non-coding RNA,lncRNA)是一类长度超过200个核苷酸的非编码RNA,在染色体修饰、转录调控以及转录后加工的水平调控基因的表达,从而影响肿瘤细胞的发生、发展.Wnt/β-catenin信号通路是一条进化上十分保守的信号通路,其异常激活时主要通过下游靶基因如c-Myc、CyclinD1等影响肿瘤的形成和进展.近年来许多研究表明lncRNA与Wnt/β-catenin通路的相互作用对消化道肿瘤的增殖、迁移、侵袭和耐药性等方面产生重要影响.对lncRNA与Wnt/β-catenin通路在消化道肿瘤中的相互作用机制研究的总结,有望为消化道肿瘤的个体化治疗提供新的治疗靶点.

Long noncoding RNAs (lncRNAs) have emerged as important regulators in the development and progression of gastric cancer (GC). ARHGAP27P1 is a pseudogene-derived lncRNA, and it has been found to be associated with GC in our preliminary study, but this association has not been studied further. Herein, we confirmed that ARHGAP27P1 was significantly downregulated in GC tissues, plasma and cells. Low expression of ARHGAP27P1 was closely associated with advanced TNM stage, increased invasion depth and lymphatic metastasis. Low ARHGAP27P1 expression also predicted a poor prognosis in GC patients. Functionally, overexpression of ARHGAP27P1 inhibited proliferation, invasion, and migration in GC cells, while silencing of ARHGAP27P1 showed the opposite effects. Mechanistic investigations showed that ARHGAP27P1 had a key role in G0/G1 arrest. We further demonstrated that ARHGAP27P1 was associated with Jumonji-domain containing 3 (JMJD3) and that this association was required for the demethylation of H3K27me3, thereby epigenetically activating expression of p15, p16 and p57. Moreover, knockdown of JMJD3, p15, or p16 consistently reversed the inhibitory effects of ARHGAP27P1 in cell proliferation and cell cycle progression. Taken together, these results suggest that lncRNA ARHGAP27P1, as a novel cell cycle regulator, may serve as a potential target for GC prevention and treatment in human GC.