Issue (7): 801-812中国科学院微生物研究所，中国微生物学会，中国菌物学会
文章信息
- 朱鹤然, 欧阳晶, 陈吉龙. 2015
- Heran Zhu, Jing Ouyang, Long Chen. 2015
- 长链非编码RNA在肿瘤发生和天然免疫中的功能与调控机制
- Function and regulation of long non-coding RNAs in tumorigenesis and host innate immunity-A review
- 微生物学报, 2015,55(7): 801-812
- Acta Microbiologica Sinica, 2015,55(7): 801-812
-
文章历史
- 收稿日期：2015-02-13
- 修回日期：2015-04-14
引用本文 |
2. 中国科学院微生物研究所, 中国科学院病原微生物与免疫学重点实验室, 北京 100101
2. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
随着ENCODE(Encyclopedia of DNA Elements)项目的开展，人们发现人类基因组中超过90%的DNA均能被转录为RNA，而其中不到2%的基因转录产物被翻译为蛋白质，其余98%的DNA转录产物为编码能力极低或无编码功能的非编码RNA(non-coding RNA,ncRNA)[1]。在ncRNA中，除tRNA、rRNA等为人熟知外，其余大量ncRNA一直被视作转录过程的“暗物质”而未受重视。近来研究证实，ncRNA可形成复杂的二级或者三级结构，通过与DNA、RNA或者蛋白质相互结合，在细胞分化和代谢等生命活动中发挥举足轻重的作用[2]。根据ncRNA的长度，将ncRNA分为小非编码RNA和长链非编码RNA(long non-coding RNA，lncRNA)，后者碱基长度在200 nt到100000 nt之间。lncRNA由RNA聚合酶Ⅱ(RNA polⅡ)或者RNA聚合酶Ⅲ(RNA pol Ⅲ)转录产生，可定位在细胞质或者细胞核，其表达具有组织特异性或发育阶段特异性等特征[3]。lncRNA既参与表观遗传、可变剪接、入核转运等过程，也能作为小RNA前体发挥功能，其转录和功能失调往往伴随着疾病的发生[4]。
1 长链非编码RNA的分类目前lncRNA还没有一个规范的分类方法，只是研究者根据其作用特点、结构特点、作用形式等进行分类。根据它们不同的特性可分为不同的类别：依据lncRNA作用特点分为转录调节lncRNA和转录后调节lncRNA；依据lncRNA的基因组定位可分为基因间lncRNA和内含子lncRNA、正义lncRNA和反义lncRNA；依据lncRNA的作用形式分为顺式lncRNA和反式lncRNA[5, 6]。
2 长链非编码RNA的作用机制长链非编码RNA可以在表观遗传修饰水平、转录水平、转录后加工以及翻译水平等多个层面上(图 1)，参与调控基因的表达[7]。
2.1 表观遗传修饰调控
表观遗传指在基因组DNA序列不发生改变的情况下，基因表达发生改变，该现象普遍存在于动植物中，例如DNA甲基化、基因组印迹和基因沉默等。lncRNA主要通过对目的基因的表观遗传修饰来完成表观遗传调控。lncRNA参与的表观遗传修饰调控过程中，与lncRNA互作的组蛋白修饰复合体主要为PRC1和PRC2复合体。例如lncRNA ANRIL可以招募PRC1复合体到INK4A/ARF基因簇，从而抑制基因的转录[8]。lncRNA Xist通过和lncRNA HOTAIR相似的机制，招募并结合PRC2复合体，介导基因沉默[9]。除了PRC复合体之外，lncRNA还与其他的组蛋白修饰复合体相互作用，调控基因的转录。例如lncRNA AIR能够与H3K9组蛋白甲基转移酶G9a相互作用，通过影响组蛋白甲基化，抑制基因的转录[10]。此外，有些lncRNA可以与一种以上的组蛋白修饰复合体相互作用，例如lncRNA HOTAIR(HOX transcript antisense RNA)5′末端有PRC2结合区，3′末端有LSD1/CoREST1结合区，HOTAIR能作为支架招募并结合相应复合体，参与基因的表观遗传调控[11]。
2.2 转录调控在已知作用机制的lncRNA中，大部分通过调控转录水平而发挥其功能。lncRNA可以占据转录因子的结合位点，抑制基因转录和表达，也可以招募转录因子到启动子或增强子上，促进基因的转录和表达。例如lncRNA DHFR上游转录产物(DHFR upstream transcripts)与二氢叶酸还原酶(dihydrofolate reductase，DHFR)基因启动子通过互补序列结合阻碍转录因子IIB结合DHFR启动子并抑制转录[13]。在小鼠细胞内，lncRNA Evf2由启动子区域转录而来，它可以招募转录因子DLX2结合到增强子上，从而诱导邻近蛋白编码基因的转录。除此之外，lncRNA还可以通过与转录因子或转录复合物基本组分相互作用影响基因的转录。例如在静息细胞中，位于细胞质中的lncRNA NRON与KPNB1、CSE1L、IQGAP1、CK1、GSK3、DYRK几个蛋白互作形成RNA-蛋白复合物，干扰NFAT1转录因子的活化以及入核，从而抑制转录[14]。热激(heat shock)产生的Alu元件能够与RNA聚合酶Ⅱ结合，抑制转录起始复合体的形成[15]。
2.3 转录后加工lncRNA对转录后mRNA剪接和加工过程的调控有多种模式。第一种，lncRNA通过与正义链mRNA碱基配对形成RNA-RNA双链，改变mRNA的剪接模式。例如MYC反义lncRNA与神经母细胞瘤MYC的mRNA形成双链，抑制剪接[16]。第二种，通过调节剪接因子的活性来调控mRNA剪接模式。例如lncRNA MALAT1与SR蛋白相互作用，进而调控SR及其他剪接因子在核斑点区域中的分布，并通过调节SR磷酸化水平影响mRNA前体的选择性剪接[17]。第三种，除了调节mRNA剪接模式，还有一类反义lncRNA，能够指导与其重叠的mRNA的编辑。这类lncRNA与mRNA形成双链RNA，在ADAR酶的催化下，将腺苷酸变为次黄苷酸，这种转变能影响RNA结构、编码潜能和microRNA的靶定。例如在黑腹果蝇中，lncRNA Sas10能够影响与之部分重叠的Rnp4F(RNA-binding protein 4F)mRNA的编辑[18]。
2.4 翻译调控除了转录后加工，lncRNA还以多种模式参与蛋白质的翻译调控。第一种模式，lncRNA能直接调控翻译过程。例如酵母中肌醇磷酸合成酶KCS1的反义lncRNA调控同一基因位点的KCS1 mRNA的翻译，合成截短的活性缺失蛋白[19]。第二种，lncRNA能调节mRNA的稳定性。例如BACE1AS是来源于BACE1(beta-site APP-cleaving enzymeⅠ)基因位点的反义lncRNA。BACE1AS与BACE1 mRNA形成RNA双链增加了mRNA的稳定性，进而解除了miRNA的降解作用[20]。第三种，属于内源竞争性RNA(competing endogenous RNAs，ceRNA)的lncRNA竞争性地与miRNA互补配对结合，从而阻止miRNA介导的降解作用，保护靶mRNA。例如在Bcr-Abl诱导细胞转化的过程中，由于lncRNA-BGL3(Beta Globin Locus 3)和PTEN具有相同的miRNA反应元件(miRNA response elements，MREs)，lncRNA-BGL3竞争性结合这些miRNA，降低了这些miRNA对PTEN的抑制作用，从而调控PTEN的水平[21]。
3 lncRNA与肿瘤发生从分子层面来说，肿瘤是抑癌基因或致癌基因异常作用的基因疾病。越来越多的研究证明，lncRNA的异常表达和调控与肿瘤发生、发展密切相关。
3.1 致癌lncRNAsPCAT-1：在前列腺癌组织中lncRNA PCAT-1(prostate cancer associated transcript 1)特异性地高表达，而且其高表达能够显著促进肿瘤细胞的生长和增殖[22]。PCAT-1的表达受PRC2复合体的负调控，其中的组蛋白甲基转移酶EZH2和SUZ12均起着重要作用。目前研究已证实，PCAT-1主要作为转录抑制因子而发挥促癌作用，可调控一系列肿瘤相关基因的表达，如CENPF，BRCA2和CENPE等[23]。
UCA1：在静息细胞里，hnRNP I与p27(Kip1) mRNAs的5′-UTR相互作用来增强其蛋白翻译水平，进而抑制细胞增殖，阻断细胞生长于G1期。而在乳腺癌细胞中，lncRNA UCA1(urothelial cancer associated 1)与hnRNP I形成一个稳定的功能性lncRNA-蛋白(核糖核蛋白)复合物，进而竞争性地抑制了p27蛋白的表达，解除了细胞增殖的抑制，导致其促癌作用[24]。
3.2 抑癌lncRNAslinc-p21：p53是重要的肿瘤抑制基因，其作用机制多样，不仅能够作为转录因子诱导基因转录，还能够作为转录抑制因子调控肿瘤相关基因的表达。Huarte等发现，p53作为转录因子直接诱导基因间长链非编码RNA p21(Long intergenic ncRNA p21，lincRNA-p21)的转录表达。而后者通过结合核不均一核糖核蛋白-K(Heterogeneous nuclear ribonucleoprotein-K，hnRNP-K)，进一步协助p53的转录抑制因子功能，促进肿瘤细胞的凋亡，发挥抑癌作用[25]。
lncRNA CCND1：细胞周期蛋白D1是一个促进细胞增殖的细胞周期调节蛋白。lncRNA CCND1的编码基因位于细胞周期蛋白D1基因的启动子区。CCND1招募并结合与DNA损伤相关的RNA结合蛋白TLS，引起TLS的变构和活化。随后TLS结合并抑制CREB结合蛋白质(CBP)和p300的组蛋白乙酰化转移酶活性，导致细胞周期蛋白D1基因的表达降低，进而抑制肿瘤的发生[26]。
3.3 兼有致癌和抑癌性质的lncRNAsH19：H19基因是最早鉴定的印迹基因之一。在许多实体瘤中，包括肝癌和膀胱癌等，都发现了lncRNA H19的异常表达。H19作为癌基因或者抑癌基因影响肿瘤的发生发展，可能与特定的肿瘤类型以及它所处的肿瘤微环境密切相关[27, 28]。在Wilms肾母细胞瘤细胞中，H19在双等位基因上的DMR区域均发生超甲基化，表达显著降低，这导致与其相邻的IGF2基因的印迹缺失(Loss of imprint,LOI)得以大量表达，并促进了肿瘤细胞的生长。H19基因很可能通过调控IGF2的印迹而抑制肿瘤的发生[29]。然而在Bcr-Abl诱导细胞转化的研究中发现，干扰lncRNA H19的表达能够促进K562细胞凋亡，并抑制细胞在裸鼠体内诱导的肿瘤生长，这显示了lncRNA H19的促癌作用[30]。
与肿瘤发生、发展密切相关的lncRNAs见表 1和表 2。
| lncRNAs | Genomic location | Expression | Function | Cancer types | Length/ kb | References |
| H19 | 11p15.5 | up | Enhance carcinogenesis and metastasis of gastric cancer. | Breast,Stomach,Bladder, Ovary,Colon etc. | 2.3 | [31, 32, 33, 34, 35] |
| HOTAIR | 12q13.13 | up | Increase cancer invasiveness and metastasis in a manner dependent on PRC2. | Breast,Ovary,Lung, Liver. | 2.2 | [36, 37, 38, 39, 40] |
| MALAT1 | 11q13.1 | up | Bind to SFPQ and release PTBP2 from the SFPQ/PTBP2 complex. | Lung,Prostate,Breast, Colon. | 8.7 | [41, 42, 43, 44] |
| PCGEM1 | 2q32 | up | Act as a coactivator for c-Myc and AR. Reprogram the androgen network and the central metabolism. | Prostate. | 1.6 | [45] |
| PCAT-1 | 8q24.21 | up | Regulate BRCA2 and control homologous recombination. Regulate c-Myc with miR-3667-3p. | Prostate,Esophageal squamous cell. | 1.9 | [23, 46, 47] |
| PTENP1 | 9p13.3 | down | Act as a ceRNA to titrate the miRNAs targeting PTEN. | Endometrium. | 3.9 | [48, 49] |
| UCA1 | 19p13.12 | up | Repress p27 (Kip1). | Esophageal squamous cell,Bladder,Breast,Tongue. | 2.3 | [24, 50, 51] |
| LncRNA-HEIH | 5q35.3 | up | Interact with EZH2. | Liver. | 1.6 | [52] |
| ANRIL | 9q21.3 | up | Repress p15(INK4b) locus and silence miR-99a/miR-449a. | Stomach,Esophageal squamous cell. | 3.8 | [53] |
| CCAT2 | 8q24.21 | up | Regulate MYC and WNT. | Stomach,Esophageal squamous cell,Breast,Colon. | 1.7 | [54, 55, 56] |
| PVT-1 | 8q24 | up | Downregulate caspase3 and smad4 expression. | Colon. | 3.0 | [57] |
| linc-p21 | 6p21.2 | up | linc-p21 induced by p53 mediates global gene repression in the p53 response. | Colon. | 3.1 | [58, 59] |
| lncRNAs | Genomic location | Expression | Function | Cancer types | Length/kb | References |
| H19 | 11p15.5 | down | Imprinted at the lgf2 locus; control igf2 expression in cis; lncRNA H19/miR-675 axis represses prostate cancer metastasis by targeting TGFBI. | Prostate,Renal. | 2.3 | [60, 29] |
| ncCCND1 | 11q13 | up | Induce TLS allosteric change and silencing cyclin D1 gene expression. | DNA damage. | 0.2 | [61] |
| Loc285194 | 3q13.31 | down | Act as a p53-regulated tumor suppressor. Repress miR211. | Bone. | 2.1 | [62, 63] |
| Loc554202 | 9p21.3 | down | Produce miR31. | Breast. | 2.2 | [64] |
| MEG3 | 14q32 | down | Mediate the effect of p53,and inhibit angiogenesis. | Ovary,Bladder,Stomach. | 1.5-9.7 | [65, 66, 67, 68] |
| linc-p21 | 6p21.2 | down | Mediate p53-dependent transcriptional repression. Inhibit JunB and CTNNB1. | Liver. | 3.1 | [69] |
| PTCSC3 | 14q13.3 | down | Act as a ceRNA of miR574-5p. | Thyroid. | 1.1 | [70] |
| RERT- lncRNA | 19q | up | RERT-lncRNA upregulated EGLN2 to affect tumorigenesis. | Liver. | 2.8 | [71] |
| lncRNA- MVIH | 10q22 | up | Inhibite phosphoglycerate kinase 1 (PGK1). | Liver. | 2.1 | [72] |
| GAS5 | 1q25.1 | down | Bind with and titrate away GR. | Breast,Cervix. | 0.6 | [73, 74, 75] |
| ncRuPAR | 5q13.3 | down | Downregulate protease-activated receptor-1. | Colon,Stomach. | 0.4 | [76, 77] |
lncRNAs在天然免疫中的作用最初于2009年被Guttman等证实。他们用LPS刺激小鼠骨髓树突状细胞后，发现有20条lncRNA表达异常。随后的基因芯片和RNA测序结果也证实了lncRNAs表达异常与小鼠肺部的病毒感染、单核细胞和巨噬细胞的激活密切相关[78]。
THRIL：THRIL基因位于编码BRI3结合蛋白(Bri3 bp)基因的下游，与Bri3 bp3’末端有部分重复序列。在细菌脂多糖LPS类似物Pam3CSK4的刺激下，THP1巨噬细胞中THRIL表达水平显著降低。Li等发现lncRNA THRIL与hnRNP L相互作用形成RNA-蛋白复合物，将结合到TNF-α和IL8、CXCL10、CCL1和CSF1的启动子上，起始转录。但当细胞外的TNFα增加到一定浓度时，则负反馈调控THRIL的转录[79]。
NEAT1：lncRNA NEAT1(Nuclear Enriched Abundant Transcript 1)又被称为病毒诱导的非编码RNA VINC(Virus Inducible NonCoding RNA)。NEAT1可被多种病毒感染所诱导表达，包括人类免疫缺陷病毒(HIV-1)、流感病毒、日本脑炎病毒、狂犬病毒和单纯疱疹病毒(HSV)。NEAT1能与蛋白NONO相互作用，促进了核内旁斑的形成。而且NEAT1能结合剪接因子SFPQ(splicing factor proline／glutamine-rich)，将SFPQ从IL8的启动子区移至旁斑中，解除了SFPQ对转录的抑制作用，从而开启抗病毒基因IL8的表达。而在HIV-1感染的细胞，lncRNA NEAT1通过促进HIV-1 mRNA从细胞核运输到细胞质，影响HIV-1的复制[80]。
lincRNA-Cox2：lincRNA-Cox2基因位于Cox2(Ptgs2)基因下游50 kb处。当树突状细胞受到细菌脂多糖LPS刺激后，lincRNA-Cox2被诱导表达。在静息的BMDM(bone marrow-derived macrophages)细胞中，lincRNA-Cox2抑制了787个基因的表达，然而在Pam3CSK4刺激后，lincRNA-Cox2诱导了713个基因的表达，其中包含大量免疫基因，例如Ccl5和IL6。虽然具体机制仍然不清楚，但lincRNA-Cox2的抑制作用依赖于其与hnRNP-A/B和hnRNP-A2/B1的结合。这些hnRNPs是多功能RNA结合蛋白家族的成员，它们在mRNA前体的加工和基因表达的调节中发挥重要作用[15]。
Lethe：Rapicavoli等发现，在小鼠胚胎成纤维细胞(MEF)中，伴随着各种病原微生物感染诱导激活TNF-α，Rps15a-ps4假基因的表达也大量增加，这个假基因叫做Lethe。促炎细胞因子选择性地诱导lncRNA Lethe的产生。而lncRNA Lethe能作为NF-κB的负反馈调节信号，通过与NF-κB RelA亚基相互作用，抑制RelA DNA结合和靶基因的激活，进而抑制由TNF-α引起的炎症反应[81]。
lnc-DC：lnc-DC只在受到病原微生物刺激后，由单核细胞分化的传统树突状细胞(conventional dendritic cells,cDCs)中特异性表达。Pin W等认为细胞质中的lnc-DC能直接结合转录因子STAT3，促进STAT3 TYR705位点的磷酸化和入核。避免了STAT3与磷酸酶SHP1结合后，STAT3的去磷酸化。持续活化的STAT3最终促进了树突状细胞分化基因的表达，进而影响着天然免疫反应[82]。
PACER：Krawczyk M等发现，在人乳腺上皮细胞和单核细胞/巨噬细胞受到细菌脂多糖LPS刺激后，CTCF(the chromatin boundary/insulator factor)打开了Cox2区域的染色质结构，导致Cox2转录起始位点上游的lncRNA PACER表达增多。lncRNA PACER和p50-p50(NF-κB的抑制形式)相互作用，进而减少了Cox2启动子区p50-p50的结合，增加了Cox2启动子区p50-p65(NF-κB的活化形式)的结合。Cox2启动子区p50-p65的结合促进p300组蛋白乙酰转移酶的招募以及RNA聚合酶II起始复合物的组装，促进Cox2的表达，进而参与炎症反应[83]。
NRAV：人源lncRNA NRAV(Negative Regulator of Anti-Viral response，又称为DYNLL1-AS1)位于染色体12q24.31。在未感染甲型流感病毒的细胞中，lncRNA NRAV通过影响一些关键干扰素刺激基因(ISGs)的组蛋白修饰(H3K4me3和H3K27me3)从而抑制这些基因的初始转录，包括重要的抗病毒效应蛋白MxA和IFITM3。而当病毒感染细胞后，宿主为了保护自身，调控lncRNA NRAV丰度下降，解除对ISG转录的抑制作用，从而促进多种ISG抗病毒蛋白的快速、大量表达。宿主通过调控NRAV而发挥的抗病毒作用，不仅仅局限于抵御甲型流感病毒感染，还被普遍应用于抵御多种其它病毒的感染，如其它RNA病毒，包括仙台病毒和呼肠孤病毒，以及DNA病毒，如单纯疱疹病毒[84]。
5 总结和展望lncRNA通过其特殊的基序或立体结构与DNA、RNA或蛋白质分子相互作用，在细胞生命活动的调控网络中发挥着重要作用。但是与小分子RNA调控功能相关的大量研究成果相比，目前针对lncRNA的研究还仅仅处于起步阶段。ENCODE的数据表明，迄今为止，该项目所收录的9640多个人类lncRNA基因位点中，人们仅对大约一百多条lncRNA进行了深入的功能研究[85, 86]，所用技术包括过表达、干扰表达、及动物模型等。因此，目前已知的关于lncRNA在肿瘤发生和天然免疫中的功能与调控机制，仅仅是lncRNA重要功能的冰山一角。此外，不断增加的转录组学研究数据表明，lncRNA表达和调控的异常还与阿尔兹海默症、自闭症、银屑病、脊髓小脑共济失调等众多疾病相关。然而，lncRNA如何参与并调控这些疾病尚不清楚。面对lncRNA复杂的作用机制，我们尚未找到可以广泛适用的规律，因而无法有效地预测lncRNA的结构与功能。
当前在进行lncRNA的研究中，人们不仅应用了传统技术，如基因组预测、cDNA文库构建、过表达、以及siRNA介导的基因沉默等，还广泛利用了许多现代高通量、高灵敏度的检测技术，如Microarray芯片分析技术和新一代高通量测序等技术。但是针对lncRNA的功能预测方面，还缺乏有效的生物信息学工具。由于lncRNA主要通过其高级结构发挥生物学作用，现有的技术方法难以对lncRNA二级结构和靶标进行有效的预测。
此外，肿瘤相关lncRNA可作为肿瘤标志物，辅助疾病的诊断和预后。异常表达的lncRNA与细胞凋亡、信号通路的激活、肿瘤转移及浸润等密切相关，从而影响肿瘤的发生与发展过程，也在一定程度上反映肿瘤的恶性发展情况。目前已发现了一些能够反映肿瘤病程的lncRNA，如lncRNA HOTAIR在乳腺癌中呈现高水平表达，可以作为肿瘤诊断的一个重要指标[87]。再如lncRNA MALAT-1是肺癌转移的标志物，并且在结肠癌、胰腺癌、乳腺癌、肝癌和前列腺癌等癌组织也发现其异常性地高表达，说明MALAT-1作为肿瘤标志物可能具有广谱性[88]。然而，相对于其它生物大分子而言，lncRNA极易被降解，所以血液中的lncRNA是否可以视为肿瘤标记物，仍值得我们进一步探讨。
近年来lncRNA已经成为国际生物与医学领域的研究热点，我们相信随着研究的广泛开展与深入，冰山之下的部分会逐渐浮出水面，人们将会发现越来越多的lncRNA参与肿瘤发生和病原微生物的致病过程，了解其在疾病发展过程中的重要作用。总之，深入了解lncRNA的功能及其分子调控机制，将有助于阐明有关疾病的发病机制。lncRNA可能作为一些疾病的分子标记物或治疗靶点，为疾病的诊断和治疗提供新契机。
| [1] | Bonasio R, Shiekhattar R. Regulation of transcription by long noncoding RNAs. Annual Review of Genetics, 2014, 48: 433-455. |
| [2] | Kung JTY, Colognori D, Lee JT. Long noncoding RNAs: Past, present, and future. Genetics, 2013, 193(3): 651-669. |
| [3] | Heuston EF, Lemon KT, Arceci RJ. The beginning of the road for non-coding RNAs in normal hematopoiesis and hematologic malignancies. Frontiers in Genetics, 2011, 2:1-9. |
| [4] | Esteller M. Non-coding RNAs in human disease. Nature Reviews Genetics, 2011, 12(12): 861-874. |
| [5] | Ma L, Bajic VB, Zhang Z. On the classification of long non-coding RNAs. RNA Biology, 2013, 10(6): 925-933. |
| [6] | Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, Lagarde J, Veeravalli L, Ruan XA, Ruan YJ, Lassmann T, Carninci P, Brown JB, Lipovich L, Gonzalez JM, Thomas M, Davis CA, Shiekhattar R, Gingeras TR, Hubbard TJ, Notredame C, Harrow J, Guigo R. The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression. Genome Research, 2012, 22(9): 1775-1789. |
| [7] | Batista PJ, Chang HY. Long noncoding RNAs: Cellular address codes in development and disease. Cell, 2013, 152(6): 1298-1307. |
| [8] | Pasmant E, Laurendeau I, Heron D, Vidaud M, Vidaud D, Bieche I. Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF. Cancer Research, 2007, 67(8): 3963-3969. |
| [9] | Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science, 2008, 322(5902): 750-756. |
| [10] | Prensner JR, Chinnaiyan AM. The emergence of lncRNAs in cancer biology. Cancer Discovery, 2011, 1(5): 391-407. |
| [11] | Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY. Long noncoding RNA as modular scaffold of histone modification complexes. Science, 2010, 329(5992): 689-693. |
| [12] | Fitzgerald KA, Caffrey DR. Long noncoding RNAs in innate and adaptive immunity. Current Opinion in Immunology, 2014, 26: 140-146. |
| [13] | Martianov I, Ramadass A, Barros AS, Chow N, Akoulitchev A. Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript. Nature, 2007, 445(7128): 666-670. |
| [14] | Sharma S, Findlay GM, Bandukwala HS, Oberdoerffer S, Baust B, Li Z, Schmidt V, Hogan PG, Sacks DB, Rao A. Dephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complex. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(28): 11381-11386. |
| [15] | Mariner PD, Walters RD, Espinoza CA, Drullinger LF, Wagner SD, Kugel JF, Goodrich JA. Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock. Molecular Cell, 2008, 29(4): 499-509. |
| [16] | Krystal GW, Armstrong BC, Battey JF. N-myc mRNA forms an RNA-RNA duplex with endogenous antisense transcripts. Molecular and Cellular Biology, 1990, 10(8): 4180-4191. |
| [17] | Tripathi V, Ellis JD, Shen Z, Song DY, Pan Q, Watt AT, Freier SM, Bennett CF, Sharma A, Bubulya PA, Blencowe BJ, Prasanth SG, Prasanth KV. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Molecular Cell, 2010, 39(6): 925-938. |
| [18] | Hundley HA, Bass BL. ADAR editing in double-stranded UTRs and other noncoding RNA sequences. Trends in Biochemical Sciences, 2010, 35(7): 377-383. |
| [19] | Nishizawa M, Komai T, Katou Y, Shirahige K, Ito T, Toh-e A. Nutrient-regulated antisense and intragenic RNAs modulate a signal transduction pathway in yeast. PLoS Biology, 2008, 6(12): 2817-2830. |
| [20] | Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, Finch CE, Laurent GS, Kenny PJ, Wahlestedt C. Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of beta-secretase. Nature Medicine, 2008, 14(7): 723-730. |
| [21] | Guo G, Kang Q, Zhu X, Chen Q, Wang X, Chen Y, Ouyang J, Zhang L, Tan H, Chen R, Huang S, Chen JL. A long noncoding RNA critically regulates Bcr-Abl-mediated cellular transformation by acting as a competitive endogenous RNA. Oncogene, 2015, 34(14): 1768-1779. |
| [22] | Prensner JR, Iyer MK, Balbin OA, Dhanasekaran SM, Cao Q, Brenner JC, Laxman B, Asangani IA, Grasso CS, Kominsky HD, Cao XH, Jing XJ, Wang XJ, Siddiqui J, Wei JT, Robinson D, Iyer HK, Palanisamy N, Maher CA, Chinnaiyan AM. Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression. Nature Biotechnology, 2011, 29(8): 742-749. |
| [23] | Prensner JR, Chen W, Iyer MK, Cao Q, Ma T, Han SM, Sahu A, Malik R, Wilder-Romans K, Navone N, Logothetis CJ, Araujo JC, Pisters LL, Tewari AK, Canman CE, Knudsen KE, Kitabayashi N, Rubin MA, Demichelis F, Lawrence TS, Chinnaiyan AM, Feng FY. PCAT-1, a long noncoding RNA, regulates BRCA2 and controls homologous recombination in cancer. Cancer Research, 2014, 74(6): 1651-1660. |
| [24] | Huang J, Zhou N, Watabe K, Lu Z, Wu F, Xu M, Mo YY. Long non-coding RNA UCA1 promotes breast tumor growth by suppression of p27 (Kip1). Cell Death & Disease, 2014, 5:e1008. |
| [25] | Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell, 2010, 142(3): 409-419. |
| [26] | Song X, Wang X, Arai S, Kurokawa R. Promoter-associated noncoding RNA from the CCND1 promoter. Methods in Molecular Biology, 2012, 809: 609-622. |
| [27] | Matouk IJ, DeGroot N, Mezan S, Ayesh S, Abu-Iail R, Hochberg A, Galun E. The H19 non-coding RNA is essential for human tumor growth. PLoS One, 2007, 2(9):e845. |
| [28] | Yoshimizu T, Miroglio A, Ripoche MA, Gabory A, Vernucci M, Riccio A, Colnot S, Godard C, Terris B, Jammes H, Dandolo L. The H19 locus acts in vivo as a tumor suppressor. Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(34): 12417-12422. |
| [29] | Taniguchi T, Sullivan MJ, Ogawa O, Reeve AE. Epigenetic changes encompassing the Igf2/H19 locus associated with relaxation of Igf2 imprinting and silencing of H19 in Wilms-Tumor. Proceedings of the National Academy of Sciences of the United States of America, 1995, 92(6): 2159-2163. |
| [30] | Guo GJ, Kang QZ, Chen QH, Chen ZL, Wang J, Tan L, Chen JL. High expression of long non-coding RNA H19 is required for efficient tumorigenesis induced by Bcr-Abl oncogene. FEBS Letters, 2014, 588(9): 1780-1786. |
| [31] | Berteaux N, Lottin V, Monte D, Pinte S, Quatannens B, Coll J, Hondermarck H, Curgy JJ, Dugimont T, Adriaenssens E. H19 mRNA-like noncoding RNA promotes breast cancer cell proliferation through positive control by E2F1. Journal of Biological Chemistry, 2005, 280(33): 29625-29636. |
| [32] | Li H, Yu B, Li J, Su L, Yan M, Zhu Z, Liu B. Overexpression of lncRNA H19 enhances carcinogenesis and metastasis of gastric cancer. Oncotarget, 2014, 5(8): 2318-2329. |
| [33] | Tsang WP, Ng EKO, Ng SSM, Jin HC, Yu J, Sung JJY, Kwok TT. Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer. Carcinogenesis, 2010, 31(3): 350-358. |
| [34] | Luo M, Li ZW, Wang W, Zeng YG, Liu ZH, Qiu JX. Upregulated H19 contributes to bladder cancer cell proliferation by regulating ID2 expression. FEBS Journal, 2013, 280(7): 1709-1716. |
| [35] | Ren C, Li X, Wang T, Wang G, Zhao C, Liang T, Zhu Y, Li M, Yang C, Zhao Y, Zhang GM. Functions and mechanisms of long noncoding RNAs in ovarian cancer. International Journal of Gynecological Cancer, 2015, DOI: 10.1097/IGC.0000000000000413. |
| [36] | Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang YL, Brzoska P, Kong B, Li R, West RB, van de Vijver MJ, Sukumar S, Chang HY. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature, 2010, 464(7291): 1071-1076. |
| [37] | Kim HJ, Lee DW, Yim GW, Nam EJ, Kim S, Kim SW, Kim YT. Long non-coding RNA HOTAIR is associated with human cervical cancer progression. International Journal of Oncology, 2015, 46(2): 521-530. |
| [38] | Qiu JJ, Wang Y, Ding JX, Jin HY, Yang G, Hua KQ. The long non-coding RNA HOTAIR promotes the proliferation of serous ovarian cancer cells through the regulation of cell cycle arrest and apoptosis. Experimental Cell Research, 2015, DOI:10.1016/j.yexcr.2015.03.005. |
| [39] | Loewen G, Jayawickramarajah J, Zhuo Y, Shan B. Functions of lncRNA HOTAIR in lung cancer. Journal of Hematology & Oncology, 2014, 7: 90. |
| [40] | Mohamadkhani A. Long noncoding RNAs in interaction with RNA binding proteins in hepatocellular carcinoma. Hepatitis Monthly, 2014, 14(5) :e18794. |
| [41] | Ji Q, Zhang L, Liu X, Zhou L, Wang W, Han Z, Sui H, Tang Y, Wang Y, Liu N, Ren J, Hou F, Li Q. Long non-coding RNA MALAT1 promotes tumour growth and metastasis in colorectal cancer through binding to SFPQ and releasing oncogene PTBP2 from SFPQ/PTBP2 complex. British Journal of Cancer, 2014, 111(4): 736-748. |
| [42] | Shen LQ, Chen L, Wang YS, Jiang XC, Xia HP, Zhuang ZX. Long noncoding RNA MALAT1 promotes brain metastasis by inducing epithelial-mesenchymal transition in lung cancer. Journal of Neuro-Oncology, 2015, 121(1): 101-108. |
| [43] | Fan Y, Shen B, Tan M, Mu X, Qin Y, Zhang F, Liu Y. TGF-beta-induced upregulation of malat1 promotes bladder cancer metastasis by associating with suz12. Clinical Cancer Research, 2014, 20(6): 1531-1541. |
| [44] | Ren SC, Liu YW, Xu WD, Sun Y, Lu J, Wang FB, Wei M, Shen J, Hou JG, Gao X, Xu CL, Huang JT, Zhao Y, Sun YH. Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer. Journal of Urology, 2013, 190(6): 2278-2287. |
| [45] | Prensner JR, Sahu A, Iyer MK, Malik R, Chandler B, Asangani IA, Poliakov A, Vergara IA, Alshalalfa M, Jenkins RB, Davicioni E, Feng FY, Chinnaiyan AM. The lncRNAs PCGEM1 and PRNCR1 are not implicated in castration resistant prostate cancer. Oncotarget, 2014, 5(6): 1434-1438. |
| [46] | Prensner JR, Chen W, Han SM, Iyer MK, Cao Q, Kothari V, Evans JR, Knudsen KE, Paulsen MT, Ljungman M, Lawrence TS, Chinnaiyan A, Feng FY. The long non-coding RNA PCAT-1 promotes prostate cancer cell proliferation through cMyc. Neoplasia, 2014, 16(11): 900-908. |
| [47] | Shi WH, Wu QQ, Li SQ, Yang TX, Liu ZH, Tong YS, Tuo L, Wang S, Cao XF. Upregulation of the long noncoding RNA PCAT-1 correlates with advanced clinical stage and poor prognosis in esophageal squamous carcinoma. Tumor Biology, 2015, DOI: 10.1007/s13277-014-2863-3. |
| [48] | Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature, 2010, 465(7301): 1033-1038. |
| [49] | Kovalenko TF, Sorokina AV, Ozolinia LA, Patrushev LI. Pseudogene PTENP1 5'-region methylation in endometrial cancer and hyperplasias. Bioorganicheskaya Khimiya, 2013, 39(4): 445-453. |
| [50] | Xue M, Li X, Li ZK, Chen W. Urothelial carcinoma associated 1 is a hypoxia-inducible factor-1 alpha-targeted long noncoding RNA that enhances hypoxic bladder cancer cell proliferation, migration, and invasion. Tumor Biology, 2014, 35(7): 6901-6912. |
| [51] | Fang ZY, Wu LM, Wang L, Yang Y, Meng YS, Yang HY. Increased expression of the long non-coding RNA UCA1 in tongue squamous cell carcinomas: a possible correlation with cancer metastasis. Oral Surgery Oral Medicine Oral Pathology Oral Radiology, 2014, 117(1): 89-95. |
| [52] | Yang F, Zhang L, Huo XS, Yuan JH, Xu D, Yuan SX, Zhu N, Zhou WP, Yang GS, Wang YZ, Shang JL, Gao CF, Zhang FR, Wang F, Sun SH. Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatology, 2011, 54(5): 1679-1689. |
| [53] | Chen DY, Zhang ZY, Mao CM, Zhou YP, Yu LC, Yin Y, Wu S, Mou X, Zhu Y. ANRIL inhibits p15(INK4b) through the TGF beta 1 signaling pathway in human esophageal squamous cell carcinoma. Cellular Immunology, 2014, 289(1-2): 91-96. |
| [54] | Ling H, Spizzo R, Atlasi Y, Nicoloso M, Shinnizu M, Redis RS, Nishida N, Gafa R, Song J, Guo ZY, Ivan C, Barbarotto E, De Vries I, Zhang XN, Ferracin M, Churchman M, van Galen JF, Beverloo BH, Shariati M, Haderk F, Estecio MR, Garcia-Manero G, Patijn GA, Gotley DC, Bhardwaj V, Shureiqi I, Sen S, Multani AS, Welsh J, Yamamoto K, Taniguchi I, Song MA, Gallinger S, Casey G, Thibodeau SN, Le Marchand L, Tiirikainen M, Mani SA, Zhang W, Davuluri RV, Mimori K, Mori M, Sieuwerts AM, Martens JWM, Tomlinson I, Negrini M, Berindan-Neagoe I, Foekens JA, Hamilton SR, Lanza G, Kopetz S, Fodde R, Calin GA. CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. Genome Research, 2013, 23(9): 1446-1461. |
| [55] | Wang CY, Hua L, Yao KH, Chen JT, Zhang JJ, Hu JH. Long non-coding RNA CCAT2 is up-regulated in gastric cancer and associated with poor prognosis. International Journal of Clinical and Experimental Pathology, 2015, 8(1): 779-785. |
| [56] | Wang J, Qiu M, Xu Y, Li M, Dong G, Mao Q, Yin R, Xu L. Long noncoding RNA CCAT2 correlates with smoking in esophageal squamous cell carcinoma. Tumor Biology, 2015, DOI: 10.1007/s13277-015-3220-x. |
| [57] | Takahashi Y, Sawada G, Kurashige J, Uchi R, Matsumura T, Ueo H, Takano Y, Eguchi H, Sudo T, Sugimachi K, Yamamoto H, Doki Y, Mori M, Mimori K. Amplification of PVT-1 is involved in poor prognosis via apoptosis inhibition in colorectal cancers. British Journal of Cancer, 2014, 110(1): 164-171. |
| [58] | Zhai HY, Fesler A, Schee K, Fodstad O, Flatmark K, Ju JF. Clinical significance of long intergenic noncoding RNA-p21 in colorectal cancer. Clinical Colorectal Cancer, 2013, 12(4): 261-266. |
| [59] | Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell, 2010, 142(3): 409-419. |
| [60] | Zhu MJ, Chen Q, Liu X, Sun Q, Zhao X, Deng R, Wang YL, Huang J, Xu M, Yan JS, Yu JX. lncRNA H19/miR-675 axis represses prostate cancer metastasis by targeting TGFBI. FEBS Journal, 2014, 281(16): 3766-3775. |
| [61] | Kurokawa R. Promoter-associated long noncoding RNAs repress transcription through a RNA binding protein TLS. RNA Infrastructure and Networks, 2011, 722: 196-208. |
| [62] | Liu Q, Huang JG, Zhou NJ, Zhang ZQ, Zhang AL, Lu ZH, Wu FT, Mo YY. LncRNA loc285194 is a p53-regulated tumor suppressor. Nucleic Acids Research, 2013, 41(9): 4976-4987. |
| [63] | Pasic I, Shlien A, Durbin AD, Stavropoulos DJ, Baskin B, Ray PN, Novokmet A, Malkin D. Recurrent focal copy-number changes and loss of heterozygosity implicate two noncoding RNAs and one tumor suppressor gene at chromosome 3q13.31 in Osteosarcoma. Cancer Research, 2010, 70(1): 160-171. |
| [64] | Augoff K, McCue B, Plow EF, Sossey-Alaoui K. miR-31 and its host gene lncRNA LOC554202 are regulated by promoter hypermethylation in triple-negative breast cancer. Molecular Cancer, 2012, 11. |
| [65] | Zhou Y, Zhong Y, Wang Y, Zhang X, Batista DL, Gejman R, Ansell PJ, Zhao J, Weng C, Klibanski A. Activation of p53 by MEG3 non-coding RNA. Journal of Biological Chemistry, 2007, 282(34): 24731-24742. |
| [66] | Sheng XJ, Li JQ, Yang L, Chen ZY, Zhao Q, Tan LY, Zhou YQ, Li J. Promoter hypermethylation influences the suppressive role of maternally expressed 3, a long non-coding RNA, in the development of epithelial ovarian cancer. Oncology Reports, 2014, 32(1): 277-285. |
| [67] | Ying L, Huang YR, Chen HG, Wang YW, Xia L, Chen YH, Liu YD, Qiu F. Downregulated MEG3 activates autophagy and increases cell proliferation in bladder cancer. Molecular Biosystems, 2013, 9(3): 407-411. |
| [68] | Sun M, Xia R, Jin FY, Xu TP, Liu ZJ, De W, Liu XH. Downregulated long noncoding RNA MEG3 is associated with poor prognosis and promotes cell proliferation in gastric cancer. Tumor Biology, 2014, 35(2): 1065-1073. |
| [69] | Wilusz CJ, Wilusz J. HuR and translation-the missing linc(RNA). Molecular Cell, 2013, 52(1): 153-153. |
| [70] | Fan M, Li XY, Jiang W, Huang Y, Li JD, Wang ZM. A long non-coding RNA, PTCSC3, as a tumor suppressor and a target of miRNAs in thyroid cancer cells. Experimental and Therapeutic Medicine, 2013, 5(4): 1143-1146. |
| [71] | Zhu ZS, Gao XR, He Y, Zhao H, Yu Q, Jiang D, Zhang PZ, Ma XP, Huang HX, Dong D, Wan J, Gu ZY, Jiang XH, Yu L, Gao YZ. An insertion/deletion polymorphism within RERT-lncRNA modulates hepatocellular carcinoma risk. Cancer Research, 2012, 72(23): 6163-6172. |
| [72] | Yuan SX, Yang F, Yang Y, Tao QF, Zhang J, Huang G, Yang Y, Wang RY, Yang S, Huo XS, Zhang L, Wang F, Sun SH, Zhou WP. Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients' poor recurrence-free survival after hepatectomy. Hepatology, 2012, 56(6): 2231-2241. |
| [73] | Kino T, Hurt DE, Ichijo T, Nader N, Chrousos GP. Noncoding RNA gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Science Signaling, 2010, 3(107):ra8. |
| [74] | Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene, 2009, 28(2): 195-208. |
| [75] | Cao S, Liu W, Li F, Zhao W, Qin C. Decreased expression of lncRNA GAS5 predicts a poor prognosis in cervical cancer. International Journal of Experimental Pathology, 2014, 7(10): 6776-6783. |
| [76] | Liu L, Yan B, Yang ZH, Zhang XD, Gu QH, Yue XQ. ncRuPAR inhibits gastric cancer progression by down-regulating protease-activated receptor-1. Tumor Biology, 2014, 35(8): 7821-7829. |
| [77] | Yan B, Gu W, Yang ZH, Gu Z, Yue XQ, Gu QH, Liu L. Downregulation of a long noncoding RNA-ncRuPAR contributes to tumor inhibition in colorectal cancer. Tumor Biology, 2014, 35(11): 11329-11335. |
| [78] | Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature, 2009, 458(7235): 223-227. |
| [79] | Li ZH, Chao TC, Chang KY, Lin NW, Patil VS, Shimizu C, Head SR, Burns JC, Rana TM. The long noncoding RNA THRIL regulates TNF alpha expression through its interaction with hnRNPL. Proceedings of the National Academy of Sciences of the United States of America, 2014, 111(3): 1002-1007. |
| [80] | Imamura K, Imamachi N, Akizuki G, Kumakura M, Kawaguchi A, Nagata K, Kato A, Kawaguchi Y, Sato H, Yoneda M, Kai C, Yada T, Suzuki Y, Yamada T, Ozawa T, Kaneki K, Inoue T, Kobayashi M, Kodama T, Wada Y, Sekimizu K, Akimitsu N. Long noncoding RNA NEAT1-dependent SFPQ relocation from promoter region to paraspeckle mediates IL8 expression upon immune stimuli. Molecular Cell, 2014, 54(6): 1055-1055. |
| [81] | Rapicavoli NA, Qu K, Zhang JJ, Mikhail M, Laberge RM, Chang HY. A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics. Elife, 2013, 2:e00762. |
| [82] | Wang P, Xue YQ, Han YM, Lin L, Wu C, Xu S, Jiang ZP, Xu JF, Liu QY, Cao XT. The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science, 2014, 344(6181): 310-313. |
| [83] | Krawczyk M, Emerson BM. p50-associated COX-2 extragenic RNA (PACER) activates COX-2 gene expression by occluding repressive NF-kappaB complexes. Elife, 2014, 3: e01776. |
| [84] | Ouyang J, Zhu X, Chen Y, Wei H, Chen Q, Chi X, Qi B, Zhang L, Zhao Y, Gao GF, Wang G, Chen JL. NRAV, a long noncoding RNA, modulates antiviral responses through suppression of interferon-stimulated gene transcription. Cell Host & Microbe, 2014, 16(5): 616-626. |
| [85] | Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, Xue CH, Marinov GK, Khatun J, Williams BA, Zaleski C, Rozowsky J, Roder M, Kokocinski F, Abdelhamid RF, Alioto T, Antoshechkin I, Baer MT, Bar NS, Batut P, Bell K, Bell I, Chakrabortty S, Chen X, Chrast J, Curado J, Derrien T, Drenkow J, Dumais E, Dumais J, Duttagupta R, Falconnet E, Fastuca M, Fejes-Toth K, Ferreira P, Foissac S, Fullwood MJ, Gao H, Gonzalez D, Gordon A, Gunawardena H, Howald C, Jha S, Johnson R, Kapranov P, King B, Kingswood C, Luo OJ, Park E, Persaud K, Preall JB, Ribeca P, Risk B, Robyr D, Sammeth M, Schaffer L, See LH, Shahab A, Skancke J, Suzuki AM, Takahashi H, Tilgner H, Trout D, Walters N, Wang H, Wrobel J, Yu YB, Ruan XA, Hayashizaki Y, Harrow J, Gerstein M, Hubbard T, Reymond A, Antonarakis SE, Hannon G, Giddings MC, Ruan YJ, Wold B, Carninci P, Guigo R, Gingeras TR. Landscape of transcription in human cells. Nature, 2012, 489(7414): 101-108. |
| [86] | Banfai B, Jia H, Khatun J, Wood E, Risk B, Gundling WE, Kundaje A, Gunawardena HP, Yu YB, Xie L, Krajewski K, Strahl BD, Chen X, Bickel P, Giddings MC, Brown JB, Lipovich L. Long noncoding RNAs are rarely translated in two human cell lines. Genome Research, 2012, 22(9): 1646-1657. |
| [87] | Yamamoto S, Han W, Kim Y, Du L, Jamshidi N, Huang D, Kim JH, Kuo MD. Breast cancer: radiogenomic biomarker reveals associations among dynamic contrast-enhanced MR imaging, long noncoding RNA, and metastasis. Radiology, 2015, 275(2): 384-391. |
| [88] | Schmidt LH. The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth. Journal of Thoracic Oncology, 2012, 7(7): 1206. |