Long ncRNA expression associates with tissue-specific enhancers

Long non-coding RNAs (ncRNA) have recently been demonstrated to be expressed from a subset of enhancers and to be required for the distant regulation of gene expression. Several approaches to predict enhancers have been developed based on various chromatin marks and occupancy of enhancer-binding proteins. Despite the rapid advances in the field, no consensus how to define tissue specific enhancers yet exists. Here, we identify 2,695 long ncRNAs annotated by ENCODE (corresponding to 28% of all ENCODE annotated long ncRNAs) that overlap tissue-specific enhancers. We use a recently developed algorithm to predict tissue-specific enhancers, PreSTIGE, that is based on the H3K4me1 mark and tissue specific expression of mRNAs. The expression of the long ncRNAs overlapping enhancers is significantly higher when the enhancer is predicted as active in a specific cell line, suggesting a general interdependency of active enhancers and expression of long ncRNAs. This dependency is not identified using previous enhancer prediction algorithms that do not account for expression of their downstream targets. The predicted enhancers that overlap annotated long ncRNAs generally have a lower ratio of H3K4me1 to H3K4me3, suggesting that enhancers expressing long ncRNAs might be associated with specific epigenetic marks. In conclusion, we demonstrate the tissue-specific predictive power of PreSTIGE and provide evidence for thousands of long ncRNAs that are expressed from active tissue-specific enhancers, suggesting a particularly important functional relationship between long ncRNAs and enhancer activity in determining tissue-specific gene expression.     

基于RNA-Seq的长非编码RNA预测

随着新一代生物技术和生物信息学的发展,研究发现,在真核生物转录组中存在大量长非编码RNA(long non-codingRNA,lncRNA),而这些lncRNA可能在基因表达调控过程中起到关键性的功能作用.当前lncRNA研究主要采用高通量RNA-Seq测序技术,并通过生物信息学方法对测序数据进行处理和分析,以挖掘其中lncRNA的序列、结构、表达及功能等信息.本文将对基于RNA-Seq的lncRNA预测流程进行介绍,对其中涉及的生物信息学方法进行较为全面的综述,就相关问题和挑战展开讨论,并对研究进行展望.     

长链非编码RNA与细胞多向分化

本文重点概述LncRNA参与细胞分化的相关机制,列举了LncRNA在不同细胞系中参与调控的各种作用方式,如LncRNA参与维持胚胎干细胞多潜能状态、胚胎干细胞分化、神经细胞分化、肌肉分化、表皮细胞分化、成骨细胞分化、脂肪生成的机制等.     

综述: 长链非编码RNA对动脉粥样硬化等疾病影响的研究新进展

动脉粥样硬化是一种以胆固醇等脂质代谢紊乱为主要特征的病理过程,严重影响人类健康．随着遗传学和生物信息学研究的发展,曾被认为无作用的非编码基因序列逐步受到研究者的关注．长链非编码RNA(lncRNA)通过表观遗传调控、转录调控和转录后调控等途径参与剂量补偿效应、基因组印记、细胞发育分化等重要生物学过程,从而影响人类的生长发育、代谢、衰老及疾病等进程．最新研究发现,lncRNA可参与血管内皮细胞的损伤与修复、血管平滑肌细胞的增殖与迁移、巨噬细胞胆固醇的流出与炎症反应、脂质的沉积与斑块的形成等过程,从而影响动脉粥样硬化及其他心血管疾病的发生与发展．     

长链非编码RNA UCA1与肿瘤耐药

作为针对恶性肿瘤的有效治疗方式,化疗已被广泛用于治疗各种恶性肿瘤。虽然化学治疗提高了患者的存活率及预后水平,但肿瘤迅速形成的多药耐药会导致治疗失败。近年发现,作为促多药耐药基因的lncRNA UCA1介导多种肿瘤形成耐药。该文回顾了UCA1在肿瘤耐药中的研究进展,并展望了该领域未来的发展及面临的挑战。     

Long noncoding RNAs expression in gastric cancer

Long noncoding RNAs (lncRNAs) have been involved in the pathogenesis of several human cancers including gastric cancer. In the current study, we selected five lncRNAs namely NEAT1, TUG1, PANDA, UCA1, and GHET1 to assess their expressions in gastric cancer samples compared with adjacent noncancerous tissues (ANCTs) from the same patients. Some previous reports have shown contribution of these lncRNAs in gastric cancer. However, we aimed to explore their associations with patients’ clinicopathological data and their potential as diagnostic biomarkers. Significant associations were found between site of primary tumor and relative expression of all lncRNAs in cancer samples compared with ANCTs. Besides, GHET1 relative expression was associated with lymph node status. The diagnostic power of GHET1 was higher from other lncRNAs. Combination of GHET1, TUG1, UCA1, and PANDA increased the diagnostic power and significance (AUC = 0.8; P < 0.0001). The current study supports participation of lncRNAs in the pathogenesis of gastric cancer and highlights their potential as diagnostic biomarkers.     

长链非编码RNA-重编码调控因子与肿瘤的研究进展

长链非编码RNA(LncRNA)是一类长度超过200核苷酸且不编码蛋白质的RNA分子。肿瘤基因组学的快速发展使LncRNA在人类肿瘤研究方面的功能更加显著。基因间LncRNA(LincRNA)-重编码调控因子(ROR)作为一种新型LncRNA,其作用机制在结直肠癌、胰腺癌、乳腺癌的发生发展过程中有报道。我们就LincRNA-ROR在肿瘤中的相关调控机制以及在不同肿瘤中的研究现状做简要综述,以便对其有进一步了解。     

长链非编码RNA、焦亡和心肌缺血-再灌注损伤

急性心肌梗死后的再灌注是挽救缺血心肌的唯一方法,但是血流的恢复可能导致心肌缺血-再灌注损伤. 长链非编码RNA(lncRNA)和焦亡都参与了心肌缺血-再灌注损伤的病理过程并发挥重要作用. lncRNA能直接或者间接作用于焦亡信号通路相关蛋白质,对包括心肌缺血-再灌注损伤在内的多种病理过程进行调控. 本文就lncRNA和焦亡在心肌缺血-再灌注损伤中的作用做一综述,以进一步探索两者关系,为防治心肌缺血-再灌注损伤提供新思路.     

长链非编码RNA表征及其在结直肠癌发生发展中的作用和临床意义

长非编码RNA（long non-coding RNAs, lncRNAs）是一类转录本长度大于200个核苷酸,不具有蛋白质编码功能的非编码RNA（non-coding RNA, ncRNA）。人类基因组中,ncRNA基因占比超过90%,数量远大于蛋白质编码基因。作为生物大分子,lncRNA具有特定的初级和高级结构,在基因表达调控等生物学进程中发挥着特有的功能。lncRNA数量多,结构各异,因此鉴定和表征新的lncRNA,探索其结构和功能,是当前基因研究领域的热点之一。在临床疾病机制研究中,大量结果表明,lncRNA与临床疾病发生发展,特别是肿瘤的发生发展具有密切的相关性。伴随着后基因组学时代基因鉴定和功能探索方法的不断进步,探索lncRNA在疾病发生中的功能及表达变化,深入解锁lncRNA在疾病发生中涉及的分子机制,将为疾病早期预防、诊断和预后提供有效参考。基于以上的研究大背景,本文对lncRNA的定义、基因鉴定的策略和方法,高级结构检测及其对应的生物学功能,以及lncRNA的分类进行了阐述;另一方面,基于lncRNA与肿瘤发生发展的密切关系,本文以经典抑癌基因p53为切入点,对多种p53相关的lncRNA在结直肠癌（colorectal cancer, CRC）发生发展中的作用进行了归纳小结,阐述了lncRNA在结直肠癌中的表达变化、涉及的分子互作机制和信号通路,对其作为分子标志物在临床中的应用潜力进行了评估。我们乐观地认为,作为生物分子标志物,lncRNA将为包括癌症在内的疾病治疗提供全新、精准和个性化的分子靶点。     

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。     

Long non-coding RNA AK085865 ablation confers susceptibility to viral myocarditis by regulating macrophage polarization

Accumulating evidence indicates that regulators of macrophage polarization may exert pivotal functions in the development of coxsackievirus B3 (CVB3)-induced viral myocarditis (VM). However, the mechanisms underlying macrophage polarization remain to be explored. Here, we sought to identify novel and functionally important long non-coding RNAs (lncRNAs) during macrophage polarization and to investigate their function and contribution to VM. In this study, we identified the lncRNA AK085865 as an important regulator of macrophage polarization. Knock-down of AK085865 diminished phenotypical expression of M2 macrophages while promoting polarization to the M1 phenotype. Moreover, AK085865^−/− mice had increased susceptibility to CVB3-induced VM. We observed striking bias towards M1 macrophages, whereas the M2 population was decreased in AK085865^−/− VM mice. Collectively, our findings uncover a critical role of AK085865 in the regulation of macrophage polarization in vitro and in vivo, identifying a new player in the development of VM and providing a potential clinically significant therapeutic target.     

长链非编码RNA的免疫调节机制研究进展

真核生物的基因表达受多个层面调控,包括染色体水平、DNA水平、转录水平和转录后水平的调控等.长链非编码RNA(lnc RNA)是一类转录本超过200 nt的非编码RNA,其对基因表达的调控涉及上述各个层面,如组蛋白修饰、DNA甲基化的调控、转录的促进和抑制、m RNA的剪辑及对转录因子的调控等.其作用方式复杂多样,可与DNA、mRNA和蛋白质等相互作用而发挥调节作用.LncRNA保守性较差,但其表达却有较高的细胞、组织和分化阶段特异性.免疫系统的发育和分化受到精密的调控,且具有较高的阶段性和特异性.因此研究lnc RNA的功能及作用机制,免疫系统是较好的选择,这能促进我们对免疫调控的理解,为免疫性疾病的治疗提供新的思路和方法.本文主要介绍lnc RNA的分类和lnc RNA作用的一般分子机制,及其对T细胞、B细胞、固有免疫细胞和炎症因子的分子调控机制及其进展.     

长链非编码RNAs与妇科肿瘤

长链非编码RNAs(long non-codiong RNAs,lncRNAs)是具有原始或是剪切转录本功能的RNA,并不符合小分子RNAs和结构RNAs的已知定义。它们分别在宫颈癌、卵巢癌、子宫内膜癌、乳腺癌等妇科肿瘤中出现异常表达的现象,使其有希望成为未来妇科肿瘤的新型标志物和治疗靶点,但其作用机制有待于进一步探索。     

长链非编码RNA的功能与疾病治疗的潜力

人类基因组转录本长度>200 nt（核苷酸）、不编码蛋白质的RNA分子为长链非编码RNA（long non-coding RNA,lncRNA)。lncRNA可在多个层面调节基因表达,其功能失调与包括肿瘤在内的很多人类疾病密切相关。本文概述lncRNA的种类、功能与疾病的关系,讨论基于lncRNA基因编辑、干细胞修饰及其与miRNA、蛋白质相互作用等的治疗潜能。     

Overexpression of Long Non-Coding RNA HOTAIR Promotes Tumor Growth and Metastasis in Human Osteosarcoma

Human osteosarcoma usually presented a high tendency to metastatic spread and caused poor outcomes, however, the underlying mechanism was still largely unknown. In the present study, using a series of in vitro experiments and an animal model, we investigated the roles of HOX antisense intergenic RNA (HOTAIR) during the proliferation and invasion of osteosarcoma. According with our results, HOTAIR was commonly overexpressed in osteosarcoma, which significantly correlated with advanced tumor stage, highly histological grade and poor prognosis. In vitro and in vivo experiments demonstrated that knockdown of HOTAIR could notably suppress cellular proliferation, inhibit invasion and decrease the secretion of MMP2 and MMP9 in osteosarcoma. Collectively, our results suggested that HOTAIR might be a potent therapeutic target for osteosarcoma.