Targeting the Oncogenic Long Non-coding RNA SLNCR1 by Blocking Its Sequence-Specific Binding to the Androgen Receptor

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Senescence-associated Long Non-coding RNA (SALNR) Delays Oncogene-induced Senescence through NF90 Regulation

Long non-coding RNAs (lncRNAs) have recently emerged as key players in many physiologic and pathologic processes. Although many lncRNAs have been identified, few lncRNAs have been characterized functionally in aging. In this study, we used human fibroblast cells to investigate genome-wide lncRNA expression during cellular senescence. We identified 968 down-regulated lncRNAs and 899 up-regulated lncRNAs in senescent cells compared with young cells. Among these lncRNAs, we characterized a senescence-associated lncRNA (SALNR), whose expression was reduced during cellular senescence and in premalignant colon adenomas. Overexpression of SALNR delayed cellular senescence in fibroblast cells. Furthermore, we found that SALNR interacts with NF90 (nuclear factor of activated T-cells, 90 kDa), an RNA-binding protein suppressing miRNA biogenesis. We demonstrated that NF90 is a SALNR downstream target, whose inhibition led to premature senescence and enhanced expressions of senescence-associated miRNAs. Moreover, our data showed that Ras-induced stress promotes NF90 nucleolus translocation and suppresses its ability to suppress senescence-associated miRNA biogenesis, which could be rescued by SALNR overexpression. These data suggest that lncRNA SALNR modulates cellular senescence at least partly through changing NF90 activity.     

类固醇激素受体复合物的装配与核内转运

类固醇激素受体 (ＳＲ)包括糖皮质激素受体 (ＧＲ)、孕激素受体 (ＰＲ)、雌激素受体(ＥＲ)、雄激素受体 (ＡＲ)等 ,其中以前两者的研究较多。ＳＲ主要存在于类固醇激素的靶细胞胞质和胞核中 ,当细胞外液中类固醇激素通过细胞膜进入胞质后 ,它能与胞质中ＳＲ结合 ,通过胞质和胞核中ＳＲ的穿梭 ,从而调节核基因组相关产物的转录、翻译及分泌一些生物活性物质 ,以发挥类固醇激素的作用。ＳＲ在细胞内有游离形式和复合物形式 ,而且存在几种不同的复合物形式 ,它们是怎样形成以及形成后如何转运到核内的 ?本文将对此作一综述。1 .ＳＲ复合物的组…     

长链非编码RNA 在乳腺癌中的研究进展

乳腺癌是女性最常见的恶性肿瘤之一,且其发病率呈逐年上升的趋势,尽管随着诊疗技术的进步,乳腺癌的死亡率得到了实质性的降低,但它仍是女性肿瘤死亡的第二大原因,目前对乳腺癌的治疗还面临很大的挑战。长链非编码RNA(Longnon-codingRNA,LncRNA)是一类长度超过200个核苷酸的非编码RNA分子,缺乏开放的阅读框,无编码蛋白质的功能。近年来研究发现,LncRNA可能在多种恶性肿瘤的发生、发展、侵袭及转移过程中起调控作用,且目前对其与乳腺癌的关系研究较多,对LncRNA与乳腺癌相关性的研究有望为乳腺癌的诊治提供新思路。现就LncRNA在乳腺癌中的研究进展做一综述。     

2-D Structure of the A Region of Xist RNA and Its Implication for PRC2 Association

In placental mammals, inactivation of one of the X chromosomes in female cells ensures sex chromosome dosage compensation. The 17 kb non-coding Xist RNA is crucial to this process and accumulates on the future inactive X chromosome. The most conserved Xist RNA region, the A region, contains eight or nine repeats separated by U-rich spacers. It is implicated in the recruitment of late inactivated X genes to the silencing compartment and likely in the recruitment of complex PRC2. Little is known about the structure of the A region and more generally about Xist RNA structure. Knowledge of its structure is restricted to an NMR study of a single A repeat element. Our study is the first experimental analysis of the structure of the entire A region in solution. By the use of chemical and enzymatic probes and FRET experiments, using oligonucleotides carrying fluorescent dyes, we resolved problems linked to sequence redundancies and established a 2-D structure for the A region that contains two long stem-loop structures each including four repeats. Interactions formed between repeats and between repeats and spacers stabilize these structures. Conservation of the spacer terminal sequences allows formation of such structures in all sequenced Xist RNAs. By combination of RNP affinity chromatography, immunoprecipitation assays, mass spectrometry, and Western blot analysis, we demonstrate that the A region can associate with components of the PRC2 complex in mouse ES cell nuclear extracts. Whilst a single four-repeat motif is able to associate with components of this complex, recruitment of Suz12 is clearly more efficient when the entire A region is present. Our data with their emphasis on the importance of inter-repeat pairing change fundamentally our conception of the 2-D structure of the A region of Xist RNA and support its possible implication in recruitment of the PRC2 complex.     

Genome-Wide Identification of Long Non-coding RNAs in Crassostrea gigas and Their Association with Heat Stress

Marine Biotechnology - Oysters face a complex and changeable environment in the intertidal zone. Heat stress is the main cause of their mass summer deaths. Several important genes are identified to...     

长链非编码RNA HIT在肝癌中的表达及意义

目的:探讨长链非编码RNA HIT(lncRNA-HIT)在原发性肝癌中的表达及其与患者临床病理特征的相关性,寻找肝癌治疗的新靶点。方法:收集并筛选2015年1月至2018年1月在空军军医大学第一附属医院行手术治疗的80例经病理证实的肝细胞癌患者的肝癌组织和癌旁组织。采用实时定量聚合酶连反应(q RT-PCR)法检测患者手术切除的肝癌组织及相应的癌旁组织中lncRNA-HIT的表达,并分析HIT与患者临床病理参数之间的关系。结果:原发性肝癌组织中lncRNA-HIT的表达(6.17±4.38)明显高于癌旁组织(2.81±2.58),约为癌旁组织的2.20倍(P0.05),肝癌组织中HIT的表达与肝癌TNM分期、肿瘤大小和数量显著相关(P0.05),而与性别、年龄、肝硬化、HBV、AFP无显著相关性(P0.05)。结论:lncRNA-HIT在肝癌组织中呈高表达,可能在肝癌发生发展过程起重要作用,并可能作为肝癌治疗的新靶点。     

长链非编码RNA RLM通过影响AMPK的磷酸化调节HepG2细胞中的脂质沉积

长非编码RNAs（long noncoding RNAs,lncRNAs）是一类长度大于200 nt、不能编码蛋白质的RNA分子,可通过AMPK、胰岛素受体等多种信号通路,调节细胞糖脂代谢。本研究发现,HepG2细胞中一条未报道的长链非编码RNA,命名为lnc-RLM（lnc-regulate lipid metabolism）。通过敲低HepG2细胞中lnc RLM,检测细胞中甘油三脂含量及脂质代谢相关调节因子表达量。结果显示,实验组较对照组甘油三酯含量显著升高（P<0.05）;AMPK磷酸化水平显著下调,脂质合成相关因子SREBP 1c和FAS表达量上调;同时,细胞中乙酰辅酶A羧化酶（ACC）活性较对照组显著上调（P<0.05）。在lnc RLM敲低的HepG2细胞中,利用AMPK激动剂（A-769662）作用细胞24 h,结果显示,降低的AMPK磷酸化水平并不会因AMPK激动剂的作用而显著升高。本研究结果说明,HepG2细胞中敲低lnc-RLM表达量,可通过影响AMPK磷酸化水平,调节HepG2细胞中脂质沉积。这为今后研究AMPK活性调节提供新的可能,也为代谢性疾病的治疗提供了新思路。     

长链非编码RNA在神经系统发育及神经性疾病中的作用

长链非编码RNA(long non-coding RNA,lncRNA)是一类转录本长度在200至数千个核苷酸序列,且不具有蛋白质编码潜能的非编码RNA。相较于研究较多的微小RNA（microRNA,miRNA）和干扰小RNA（small interfering,siRNA）等非编码小RNA,lncRNA的许多功能仍尚不清楚。但越来越多的研究发现,lncRNA可通过多种方式调控中枢神经系统发育,包括表观遗传组蛋白甲基化、转录辅因子调控、可变剪接调控等途经。而以上途经的异常均与多种人类重大疾病的发生密切相关,例如,阿尔兹海默症（Alzheimer’s disease,AD）、自闭症（autism spectrum disorder,ASD）、精神分裂症（schizophrenia,SZ）等。本文就lncRNA在表观遗传水平、转录水平、转录后水平和翻译水平上调控神经系统发育以及其在人类神经性疾病中的作用进行综述。     

沉默长链非编码RNA Meg3损伤小鼠胰岛细胞的胰岛素分泌功能

MEG3是一种长链非编码RNA。已有研究证明,鼠源Meg3参与小鼠诱导多能干细胞、神经元和视网膜的分化过程。最新报道,MEG3在人胰岛β细胞中高表达,但其对维持成年胰岛β细胞的功能尚不清楚。本研究旨在探讨Meg3在小鼠胰岛细胞胰岛素分泌功能中的作用。实时定量PCR揭示,与Balb/c小鼠心、肝、脾、肺、肌、肾等组织/器官比较,Meg3在胰腺组织中高表达。在非糖尿病小鼠发生自发性糖尿病的第8、12周,Meg3在胰岛中的表达水平分别下调24%±8%和29%±9% (P<0.01);而当血糖升高20 mmol/L,小鼠胰岛中Meg3表达下调72%±16%(P<0.01)。在MIN6细胞中采用RNA干扰敲减Meg3的表达,在高糖浓度（20 mmol/L）刺激条件下,胰岛素分泌显著减少。小鼠静脉注射siRNA,结合血糖测定或葡萄糖耐受试验（IPGTT）显示,si-Meg3小鼠血清胰岛素水平显著下降。注射葡萄糖前血糖升高,注射葡萄糖后耐受能力降低;免疫组化分析显示,si-Meg3小鼠胰岛素阳性细胞的面积减少。实验结果提示,Meg3通过参与胰岛素的合成和分泌维持成年小鼠胰岛功能。Meg3表达失调可能参与I型糖尿病（T1DM）发病过程。     

Long Non-coding RNA HOXA10-AS Promotes Invasion and Migration of Hepatocellular Carcinoma Cells

Some studies have showed that long non-coding RNA (lncRNA) HOXA10-AS acts as an oncogene and regulates the invasion and metastasis of tumor cells. However, its mechanism in the invasion and migration of hepatocellular carcinoma (HCC) cells is unclear. The purpose of this study was to analyze the expression of HOXA10-AS in HCC tissues and its clinical significance, detect the influence of HOXA10-AS on the invasion and migration of HCC cells, and explore the mechanism of HOXA10-AS in promoting the invasion and migration of HCC cells. The results of quantitative real-time PCR (qRT-PCR) showed that the expression of HOXA10-AS was significantly upregulated in HCC tissues compared with the adjacent non-HCC tissues. Age and gender did not show significant correlation with HOXA10-AS expression, while tumor size, lymphatic metastasis and distant metastasis showed significant correlation with HOXA10-AS expression. Meanwhile, the expression of HOXA10-AS in HCC cells was higher than that in normal liver cells. After interfering with HOXA10-AS in HCC cell lines HepG2 and QGY7701, Transwell invasion and scratch experiments showed that the invasion and migration ability of HOXA10-AS cells in the HOXA10-AS group was significantly lower than that in the control group. Western blotting results showed that the expression levels of vimentin and N-cadherin were significantly lower than those of the control group, while the E-cadherin expression was significantly increased. The TGFβ1/Smads signaling pathway was inhibited after HOXA10-AS interference. In summary, HOXA10-AS promotes the invasion and migration of HCC cells by the TGFβ1/Smads signaling pathway.