Emerging roles of lncRNAs in the post-transcriptional regulation in cancer

He, Rongzhang; Luo, Dixian; Mo, Yin‐Yuan

doi:10.1016/j.gendis.2019.01.003

Cited by 198 publications

(134 citation statements)

References 91 publications

(139 reference statements)

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“…Although they are not translated into protein, lncRNAs can share similar characteristics and mechanisms found in messenger RNA (mRNA) such as alternative splicing and polyadenylation. LncRNAs exert their function as gene regulators by serving as signals, decoys, and scaffolds through a partnership with RNA binding proteins in ribonucleoprotein complexes [17].…”

mentioning

confidence: 99%

Transcriptomic profiling of PBDE-exposed HepaRG cells unveils critical lncRNA- PCG pairs involved in intermediary metabolism

Zhang

Kelly

et al. 2020

PLoS ONE

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Polybrominated diphenyl ethers (PBDEs) were formally used as flame-retardants and are chemically stable, lipophlic persistent organic pollutants which are known to bioaccumulate in humans. Although its toxicities are well characterized, little is known about the changes in transcriptional regulation caused by PBDE exposure. Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of transcriptional and translational processes. It is hypothesized that lncRNAs can regulate nearby protein-coding genes (PCGs) and changes in the transcription of lncRNAs may act in cis to perturb gene expression of its neighboring PCGs. The goals of this study were to 1) characterize PCGs and lncRNAs that are differentially regulated from exposure to PBDEs; 2) identify PCG-lncRNA pairs through genome annotation and predictive binding tools; and 3) determine enriched canonical pathways caused by differentially expressed lncRNA-PCGs pairs. HepaRG cells, which are humanderived hepatic cells that accurately represent gene expression profiles of human liver tissue, were exposed to BDE-47 and BDE-99 at a dose of 25 μM for 24 hours. Differentially expressed lncRNA-PCG pairs were identified through DESeq2 and HOMER; significant canonical pathways were determined through Ingenuity Pathway Analysis (IPA). LncTar was used to predict the binding of 19 lncRNA-PCG pairs with known roles in drug-processing pathways. Genome annotation revealed that the majority of the differentially expressed lncRNAs map to PCG introns. PBDEs regulated overlapping pathways with PXR and CAR such as protein ubiqutination pathway and peroxisome proliferator-activated receptor alpharetinoid X receptor alpha (PPARα-RXRα) activation but also regulate distinctive pathways involved in intermediary metabolism. PBDEs uniquely down-regulated GDP-L-fucose biosynthesis, suggesting its role in modifying important pathways involved in intermediary metabolism such as carbohydrate and lipid metabolism. In conclusion, we provide strong evidence that PBDEs regulate both PCGs and lncRNAs in a PXR/CAR ligand-dependent and independent manner.

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confidence: 99%

Transcriptomic profiling of PBDE-exposed HepaRG cells unveils critical lncRNA- PCG pairs involved in intermediary metabolism

Zhang

Kelly

et al. 2020

PLoS ONE

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“…Due to the heterogeneity of tumors and the complexity of the tumor microenvironment, these molecules can play a carcinogenic or tumor suppressive role in the same tumor. There is evidence that lncRNAs can act as molecular scaffolds, sponges or coactivators in tumor scaffolds by interacting with DNA, RNA or proteins [5,31,32] . At present, increasing evidence has shown that the abnormally high expression of SNHG12 plays a carcinogenic role in various malignant tumors [10][11][12][13][14][15][16][17][18][19][26][27][28][29] .…”

Section: Discussionmentioning

confidence: 99%

“…It was gradually recognized that lncRNAs are involved in transcriptional and post-transcriptional regulation by recruiting transcription factors, remodeling chromatin, splicing pre-mRNA, and acting as molecular sponges and scaffolds in multifarious diseases and tumors. These molecules act as tumor promoters or tumor suppressors in the multistep development of human tumors [5][6][7] . In addition, lncRNAs can be present in many tissues and uids for a long time, and can be used as a biomarker for extensive screening of diseases [8] .…”

Section: Introductionmentioning

confidence: 99%

Long Noncoding RNA SNHG12 is a Potential Diagnostic and Prognostic Biomarker in Various Tumors

Wang

Jiang

Zhang³

et al. 2020

Preprint

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Background. Tumors are the second most common cause of death in humans worldwide, second only to cardiovascular and cerebrovascular diseases. Although methods and techniques for the treatment of tumors continue to improve, the effect is not satisfactory. These may lack effective therapeutic targets. This study aimed to evaluate the value of SNHG12 as a biomarker in the prognosis and clinical characteristics of various cancer patients.Methods. We analyzed SNHG12 expression and plotted the survival curves of all cancer samples in the TCGA database using the GEPIA tool. Then, we searched for eligible papers up to April 1, 2019 in databases. Next, the data were extracted from studies examining SNHG12 expression, overall survival and clinicopathological features in patients with malignant tumors. We used Review Manager 5.3 and Stata 15 software to analyze the statistical data.Results. In the TCGA database, abnormally high expression of SNHG12 in tumor samples indicates that the patient has a poor prognosis. Results of meta-analysis is that SNHG12 high expression is related to low overall survival (HR=2.72, 95% CI=1.95-3.8, P<0.00001), high tumor stage (OR=3.94, 95% CI=2.80-5.53, P<0.00001), high grade (OR=2.04, 95% CI=1.18-3.51, P=0.01), distant metastasis (OR=2.20, 95% CI=1.40-3.46, P=0.0006), tumor size (OR=2.79, 95% CI=1.89-4.14, P<0.00001) and lymph node metastasis (OR=2.66, 95%CI=1.65-4.29, P<0.0001).Conclusions. Our study confirmed that the high expression level of SNHG12 is closely related to the clinicopathological characteristics and prognosis of patients and is a new predictive biomarker for various cancer patients.

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“…Importantly, many nuclear lncRNAs have been reported to reside in condensates, named collectively "membraneless compartments" [4]. A notable example are paraspeckles which comprise the lncRNA NEAT1 and RNA-binding proteins (RBPs) that influence gene expression by post-transcriptional regulation of splicing and polyadenylation [5,6], as well as by interaction with the SWI/SNF complex that remodels nucleosomes [7]. Similarly, the lncRNA MALAT1, which also forms condensates, has been shown to regulate gene expression by interactions with splicing factors [8].…”

Section: Introductionmentioning

confidence: 99%

Nucleus size and DNA accessibility are linked to the regulation of paraspeckle formation in cellular differentiation

et al. 2020

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Background: Many long noncoding RNAs (lncRNAs) have been implicated in general and cell type-specific molecular regulation. Here, we asked what underlies the fundamental basis for the seemingly random appearance of nuclear lncRNA condensates in cells, and we sought compounds that can promote the disintegration of lncRNA condensates in vivo.Results: As a basis for comparing lncRNAs and cellular properties among different cell types, we screened lncRNAs in human pluripotent stem cells (hPSCs) that were differentiated to an atlas of cell lineages. We found that paraspeckles, which form by aggregation of the lncRNA NEAT1, are scaled by the size of the nucleus, and that small DNA-binding molecules promote the disintegration of paraspeckles and other lncRNA condensates. Furthermore, we found that paraspeckles regulate the differentiation of hPSCs.Conclusions: Positive correlation between the size of the nucleus and the number of paraspeckles exist in numerous types of human cells. The tethering and structure of paraspeckles, as well as other lncRNAs, to the genome can be disrupted by small molecules that intercalate in DNA. The structure-function relationship of lncRNAs that regulates stem cell differentiation is likely to be determined by the dynamics of nucleus size and binding site accessibility.

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Emerging roles of lncRNAs in the post-transcriptional regulation in cancer

Cited by 198 publications

References 91 publications

Transcriptomic profiling of PBDE-exposed HepaRG cells unveils critical lncRNA- PCG pairs involved in intermediary metabolism

Transcriptomic profiling of PBDE-exposed HepaRG cells unveils critical lncRNA- PCG pairs involved in intermediary metabolism

Long Noncoding RNA SNHG12 is a Potential Diagnostic and Prognostic Biomarker in Various Tumors

Nucleus size and DNA accessibility are linked to the regulation of paraspeckle formation in cellular differentiation

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