Long noncoding RNAs in development and disease of the central nervous system

Ng, Shi‐Yan; Lin, Lin; Soh, Boon Seng; Stanton, Lawrence W.

doi:10.1016/j.tig.2013.03.002

Cited by 294 publications

(223 citation statements)

References 92 publications

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“…3 Recently, functional lncRNAs are recognized as critical players of gene regulation in multiple biological processes such as cell growth, development, angiogenesis and inflammation. [4][5][6][7] LncRNAs are also associated with many human diseases such as cancers, Alzheimer disease and cardiovascular diseases. 3,[8][9][10] The functional characterization of lncRNAs is however much more difficult than expected due to their poor conservation and complex mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-κB pathway

et al. 2015

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Antisense Noncoding RNA in the INK4 Locus (ANRIL) is the prime candidate gene at Chr9p21, the welldefined genetic risk locus associated with multiple human diseases including coronary artery disease (CAD), while little is known regarding its role in the pathological processes. Endothelial dysfunction triggers atherosclerotic processes that are causatively linked to CAD. To evaluate the function of ANRIL in human endothelial cells (ECs), we examined ANRIL expression under pathological stimuli and found ANRIL was markedly induced by pro-inflammatory factors. Loss-of-function and chromatin immunoprecipitation approaches revealed that NF-kB mediates TNF-a induced ANRIL expression. RNA sequencing revealed that ANRIL silencing dysregulated expression of inflammatory genes including IL6 and IL8 under TNF-a treatment. We explored the regulatory mechanism of ANRIL on IL6/8 and found that Yin Yang 1 (YY1), an ANRIL binding transcriptional factor revealed by RNA immunoprecipitation, was required for IL6/8 expression under TNF-a treatment. YY1 was enriched at promoter loci of IL6/8 and ANRIL silencing impaired the enrichment, indicating a cooperation between ANRIL and YY1 in the regulation of inflammatory genes. For the first time, we establish the connection between ANRIL and NF-kB pathway and show that ANRIL regulates inflammatory responses through binding with YY1. The newly identified TNF-a-NF-kB-ANRIL/YY1-IL6/8 pathway enhances understanding of the etiology of CAD and provides potential therapeutic target for treatment of CAD.

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Section: Introductionmentioning

confidence: 99%

Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-κB pathway

et al. 2015

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“…However, there is no effective therapy for inflammation or for DNP. LncRNAs, typically defined as transcripts longer than 200 nucleotides, are recently regarded as a potential therapeutic target for inflammatory relevant diseases, including diabetes and DNP [26][27][28][29][30][31][32][33][34][35][36][37][38]. However, the functional question of massive lncRNAs in DNP has not been characterized [26,27,30].…”

Section: Discussionmentioning

confidence: 99%

“…It is estimated that only 2 % of the mammalian genome is composed of genes that encode proteins, while the bulk is transcribed as noncoding RNA [26,27]. A large number of long noncoding RNAs (lncRNAs) are expressed in the nervous system [26,27].…”

Section: Introductionmentioning

confidence: 99%

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LncRNA NONRATT021972 siRNA attenuates P2X7 receptor expression and inflammatory cytokine production induced by combined high glucose and free fatty acids in PC12 cells

Liu

et al. 2016

Purinergic Signalling

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Diabetic neuropathy (DNP) is a frequent chronic complication of diabetes mellitus with potentially lifethreatening outcomes. High glucose and elevated free fatty acids (FFAs) have been recently recognized as major causes of nervous system damage in diabetes. Our previous study has indicated extracellular stimuli, such as high glucose and/or FFA stress, may activate the p38 mitogen-activated protein kinase (MAPK) signaling pathway and induce a p38 MAPK-dependent sensitization of the P2X7 receptor and release of inflammatory factors in PC12 cells, while the mechanisms underlying remain to be elucidated. Long noncoding RNAs (lncRNAs) play important roles in diverse biological processes, including activation of a series of pathway signalings. Here, we showed combined high D-glucose and FFAs ( H G H F ) i n d u c e d a n i n c r e m e n t o f l n c R N A -NONRATT021972 (NONCODE ID, nc021972) in PC12 cells. Nc021972 small interference RNA (siRNA) alleviated HGHF-induced activation of p38 MAPK, expression of the P2X7 receptor, and [Ca 2+ ] i increment upon P2X7 receptor activation. Further experiments showed that there existed a crosstalk between nc021972 and the p38 MAPK signaling pathway. Inhibition of p38 MAPK signaling decreased nc021972-induced expression of the P2X7 receptor and [Ca 2+ ] i increment upon P2X7 receptor activation. Also, nc021972 siRNA inhibited HGHF-induced PC12 release of TNF-α and IL-6 and rescued decreased cell viability mediated by the P2X7 receptor. Therefore, inhibition of nc021972 may serve as a novel therapeutic strategy for diabetes complicated with nervous inflammatory diseases.

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“…[1][2][3][4][5] Even though small and long ncRNAs (lncRNAs) represent the two halves of the ncRNA world, they intermingle with one another both functionally, when long RNAs control the availability and activity of small RNAs, such as microRNAs (miRNAs), 6 and structurally, when small RNAs are embedded inside lncRNA genes. In this latter case, a unique primary transcript can generate two mature RNA molecules whose expression, as well as function, may be coordinated or independent.…”

Section: Introductionmentioning

confidence: 99%

Identification of linc-NeD125, a novel long non coding RNA that hosts miR-125b-1 and negatively controls proliferation of human neuroblastoma cells

et al. 2015

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Long noncoding RNAs in development and disease of the central nervous system

Cited by 294 publications

References 92 publications

Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-κB pathway

Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-κB pathway

LncRNA NONRATT021972 siRNA attenuates P2X7 receptor expression and inflammatory cytokine production induced by combined high glucose and free fatty acids in PC12 cells

Identification of linc-NeD125, a novel long non coding RNA that hosts miR-125b-1 and negatively controls proliferation of human neuroblastoma cells

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