Identifying and functionally characterizing tissue-specific and ubiquitously expressed human lncRNAs

Jiang, Chunjie; Li, Yongsheng; Zhao, Zheng; Lu, Jianping; Chen, Hong; Ding, Na; Wang, Guangjuan; Xu, Juan; Li, Xia

doi:10.18632/oncotarget.6859

Cited by 107 publications

(73 citation statements)

References 59 publications

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“…Under normal circumstances, many lncRNAs are ubiquitously expressed across all human tissue types at a basal level and may be involved in maintaining cellular function (44). Similar to protein-coding inflammatory genes, many lncRNAs have been found to be targets of inflammatory pathways, and consequently, their expression profile is altered in various cell types during inflammation.…”

Section: Lncrnas Models Of Transcriptional Control and Expression Inmentioning

confidence: 99%

Long non-coding RNAs (lncRNAs) and their transcriptional control of inflammatory responses

Mathy

Chen

2017

Journal of Biological Chemistry

201

162

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Edited by George M. Carman Long non-coding RNAs (lncRNAs) have emerged as potential key regulators of the inflammatory response, particularly by modulating the transcriptional control of inflammatory genes. lncRNAs may act as an enhancer or suppressor to inflammatory transcription, function as scaffold molecules through interactions with RNA-binding proteins in chromatin remodeling complexes, and modulate dynamic and epigenetic control of inflammatory transcription in a gene-specific and time-dependent fashion. Here, we will review recent literature regarding the role of lncRNAs in transcriptional control of inflammatory responses. Better understanding of lncRNA regulation of inflammation will provide novel targets for the development of new therapeutic strategies.Because of the potentially destructive nature of the inflammatory response, the expression of inflammation-related genes is finely regulated at multiple levels, including transcription, mRNA processing, translation, phosphorylation, and degradation. Transcription represents an essential, and often the most important, regulatory determinant of the inflammation process. Many signaling pathways and transcription factors are involved in the inflammatory response, including the transcription factor nuclear factor-B (NF-B), 2 MAPK, and JAK/ STAT pathways, together controlling a multitude of inflammatory response genes (1, 2). Upon activation, these pathways directly activate and induce the expression of a limited set of transcription factors that promote the transcription of inflammatory genes. Whereas the mechanisms of initial activation and subsequent nuclear translocation of associated transcription factors for these signaling pathways are well-characterized, how the transcription of inflammatory genes is finely controlled in the nucleus to ensure that each individual gene is transcribed at the "right" place at the "right" time remains elusive. Perhaps this can be best represented by the inflammatory transcription induced by NF-B. The NF-B signaling cascade can be activated by inflammatory signals, including LPS, TNF-␣, IL-1␤, and reactive oxygen species, among others; many Toll-like receptors (TLRs) also activate NF-B (3-8).Prior to an activating signal, NF-B dimers are sequestered in the cytoplasm and held inactive by association with I B proteins (9). Activating stimuli cause I B degradation (10, 11), and consequently, free NF-B dimers translocate to the nucleus, bind to B sites, and promote gene transcription (12). Common targets of NF-B include inflammatory cytokines, chemokines, adhesion molecules, cytoprotective proteins, and proteins regulating cell differentiation, proliferation, and survival (13,14). In addition to its initial cytoplasmic activation, both the recruitment of NF-B to target genes in the nuclei and NF-B-induced transcriptional events after recruitment are finely controlled events to ensure proper transactivation of NF-B target genes (15). Indeed, several waves of gene transcription have been demonstrated in macrophages following LP...

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Section: Lncrnas Models Of Transcriptional Control and Expression Inmentioning

confidence: 99%

Long non-coding RNAs (lncRNAs) and their transcriptional control of inflammatory responses

Mathy

Chen

2017

Journal of Biological Chemistry

201

162

View full text Add to dashboard Cite

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“…lncRNAs are typically divided into intergenic, bidirectional, antisense, overlapping and intronic lncRNAs according to their genomic localization in relation to nearby coding genes14. A large number of lncRNAs exhibit a tissue- or cell type-specific pattern1516 and display weaker evolutionary constraints and lower expression levels than protein-coding genes17. A growing body of evidence suggests an important role of lncRNAs in cancer, including EOC.…”

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confidence: 99%

LncRNAs expression profiling in normal ovary, benign ovarian cyst and malignant epithelial ovarian cancer

Wang

Dai

et al. 2016

Sci Rep

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Long noncoding RNA (lncRNA) has been recognized as a regulator of gene expression, and the dysregulation of lncRNAs is involved in the progression of many types of cancer, including epithelial ovarian cancer (EOC). To explore the potential roles of lncRNAs in EOC, we performed lncRNA and mRNA microarray profiling in malignant EOC, benign ovarian cyst and healthy control tissues. In this study, 663 transcripts of lncRNAs were found to be differentially expressed in malignant EOC compared with benign and normal control tissues. We also selected 18 altered lncRNAs to confirm the validity of the microarray analysis using quantitative real-time PCR (qPCR). Pathway and Gene Ontology (GO) analyses demonstrated that these altered transcripts were involved in multiple biological processes, especially the cell cycle. Furthermore, Series Test of Cluster (STC) and lncRNA-mRNA co-expression network analyses were conducted to predict lncRNA expression trends and the potential target genes of lncRNAs. We also determined that two antisense lncRNAs (RP11-597D13.9 and ADAMTS9-AS1) were associated with their nearby coding genes (FAM198B, ADAMTS9), which participated in cancer progression. This study offers helpful information to understand the initiation and development mechanisms of EOC.

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“…From the early drug screens and subsequent prediction efforts, it is clear that the tissue lineage of cancer cell lines has a strong confounding effect on the drug response prediction models (Barretina et al 2012). Considering the tissue-specific expression patterns of lncRNAs (Jiang et al 2016), we emphasized the inclusion of tissue type of the cell lines as a covariate in all of our analyses. Moreover, we addressed the unique challenge of identifying drug responserelated lncRNAs that are independent of the effects of proximal cis-PCGs and well-established PCG biomarkers.…”

Section: Discussionmentioning

confidence: 99%

Discovering novel long non-coding RNA predictors of anticancer drug sensitivity beyond protein-coding genes

Nath

Lau

Lee

et al. 2019

Preprint

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Large-scale cancer cell line screens have identified thousands of protein-coding genes (PCGs) as biomarkers of anticancer drug response. However, systematic evaluation of long non-coding RNAs (lncRNAs) as pharmacogenomic biomarkers has so far proven challenging. Here, we study the contribution of lncRNAs as drug response predictors beyond spurious associations driven by correlations with proximal PCGs, tissue-lineage or established biomarkers. We show that, as a whole, the lncRNA transcriptome is equally potent as the PCG transcriptome at predicting response to hundreds of anticancer drugs. Analysis of individual lncRNAs transcripts associated with drug response reveals nearly half of the significant associations are in fact attributable to proximal cis-PCGs. However, adjusting for effects of cis-PCGs revealed significant lncRNAs that augment drug response predictions for most drugs, including those with well-established clinical biomarkers. In addition, we identify lncRNA-specific somatic alterations associated with drug response by adopting a statistical approach to determine lncRNAs carrying somatic mutations that undergo positive selection in cancer cells. Lastly, we experimentally demonstrate that two novel lncRNA, EGFR-AS1 and MIR205HG, are functionally relevant predictors of anti-EGFR drug response.3

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Identifying and functionally characterizing tissue-specific and ubiquitously expressed human lncRNAs

Cited by 107 publications

References 59 publications

Long non-coding RNAs (lncRNAs) and their transcriptional control of inflammatory responses

Long non-coding RNAs (lncRNAs) and their transcriptional control of inflammatory responses

LncRNAs expression profiling in normal ovary, benign ovarian cyst and malignant epithelial ovarian cancer

Discovering novel long non-coding RNA predictors of anticancer drug sensitivity beyond protein-coding genes

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