The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer, regulates ADIPOR1, VAMP3 and C11ORF10 (lncRNA ANRIL exon 13)
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PROVIDER: PRJNA438347 | ENA |
REPOSITORIES: ENA
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Project description:To identify genes that are regulated from the lncRNA ANRIL (EXON 13), we designed inducible short hairpin RNA constructs and stable integrated them into HEK cells Changes of gene expression after induction were determined at 48h and 96h by genome-wide mRNA expression analysis.
2018-04-09 | GSE111843 | GEO
Project description:The antisense non-coding RNA in the INK locus (ANRIL), which originates from the CDKN2A/B (INK4-ARF) locus, has been identified as a hotspot for genetic variants associated with cardiometabolic disease including coronary artery disease (CAD) and Type 2 diabetes (T2D). We recently found that ANRIL abundance in human pancreatic islets was increased in donors carrying certain T2D risk-SNPs, and that a T2D risk-SNP located within exon2 of ANRIL conferred reduced beta cell proliferation index, pointing to a role for ANRIL in the regulation of T2D pathogenicity via an impact on insulin secretory capacity. Recent studies in other cell types have found that the balance between linear and circular species of ANRIL is linked to the regulation of cardiovascular disease phenotypes. Less is known about circular ANRIL expression in diabetes-relevant cell types and how their abundance might influence the risk of T2D. Herein, we use high-throughput and divergent primer sequencing of circular RNA in human pancreatic islet cells to quantify and characterize circular isoforms of ANRIL. We identified several circular ANRIL isoforms that are more abundant than linear ANRIL and whose expression was correlated across dozens of individuals. Back-splicing did not occur with equal probability at all ANRIL splice sites. Rather, some specific splice sites were found to have a higher propensity to be involved in back-splicing and are weakly enriched for sequence features known to promote back-splicing. Finally, we found that islets from carriers of the T2D risk allele at rs564398 in exon 2 of ANRIL had a higher ratio of circular ANRIL relative to linear ANRIL compared to protective-allele carriers, and that higher circular:linear ANRIL ratio was associated with a decreased beta cell proliferation index. Together, our study points to the combined involvement of both linear and circular ANRIL species in T2D phenotypes and opens the door for future studies to understand the molecular mechanisms by which ANRIL impacts cellular function in human pancreatic islets.
2022-05-11 | GSE192541 | GEO
Project description:Circular RNAs (circRNAs) are broadly expressed in eukaryotic cells, but their role in human health and disease remains obscure. Here, we show that circular antisense non-coding RNA in the INK4 locus (circANRIL), which is transcribed at a locus of atherosclerotic cardiovascular disease on chromosome 9p21, confers athero-protection by controlling ribosomal RNA (rRNA) maturation and modulating pathways of atherogenesis. At the molecular level, circANRIL competes with precursor rRNA (pre-rRNA) for binding to pescadillo homolog 1 (PES1), an essential 60S-preribosomal assembly factor, thereby impairing exonuclease-mediated pre-rRNA processing and ribosome biogenesis. As a consequence, circANRIL induces nucleolar stress and p53 activation, resulting in the induction of apoptosis and inhibition of proliferation, which are key athero-protective cell functions within the arterial wall. Collectively, these findings identify circANRIL as a prototype of a circRNA regulating ribosome biogenesis and conferring athero-protection, thereby unveiling a therapeutic potential of certain circRNAs in human disease. Analysis of transcriptome-wide expression level in HEK293 cells with stable overexpression of circular ANRIL (n=3) compared to a vector control (n=3).
2016-08-22 | E-GEOD-65392 | biostudies-arrayexpress
Project description:Coronary artery disease (CAD) is the most common cardiovascular disease and the leading cause of death worldwide. To date, the 9p21.3 locus is the most robust and frequently replicated risk locus of CAD among >90 CAD risk loci identified by GWAS. More than 50 CAD-associated genomic variants were identified at the 9p21.3 CAD locus and many of them are located within a long non-coding gene ANRIL, which was initially referred to as Antisense Non-coding RNA in INK4 Locus. The causal role of ANRIL in CAD and the underlying molecular mechanism are unknown. We used gene expression microarray to identify the downstream target genes of ANRIL and to explore molecular mechanisms by which ANRIL might contribute to the risk development of CAD.
2019-01-16 | GSE117676 | GEO
Project description:Long non-coding RNAs (ncRNAs) are major regulators of gene expression and cell fate. The INK4 locus encodes the tumour suppressor proteins p15INK4b, p16INK4a and p14ARF required for cell cycle arrest and whose expression increases during senescence. ANRIL is a ncRNA antisense to the p15 gene. In proliferative cells, ANRIL prevents senescence by repressing INK4 genes through the recruitment of Polycomb-group proteins. In models of replicative and RASval12 oncogene-induced senescence (OIS), the expression of ANRIL and Polycomb proteins decreases, thus allowing INK4 derepression. Here, we found in a model of RAF1 OIS that ANRIL expression rather increases, due in particular to an increased stability. This led us to search for circular ANRIL isoforms, as circular RNAs are rather stable species. We found that the expression of two circular ANRIL increases in several OIS models (RAF1, MEK1 and BRAF). In proliferative cells, they repress p15 expression, while in RAF1 OIS, they promote full induction of p15, p16 and p14ARF expression. Further analysis of one of these circular ANRIL shows that it interacts with Polycomb proteins and decreases EZH2 Polycomb protein localization and H3K27me3 at the p15 and p16 promoters, respectively. We propose that changes in the ratio between Polycomb proteins and circular ANRIL isoforms allow these isoforms to switch from repressors of p15 gene to activators of all INK4 genes in RAF1 OIS. Our data reveal that regulation of ANRIL expression depends on the senescence inducer and underline the importance of circular ANRIL in the regulation of INK4 gene expression and senescence.
2020-12-31 | GSE143957 | GEO
Project description:Long non-coding RNAs（LncRNAs）have important cellular functions and some have roles in different mechanisms of gene regulation. LncRNA-antisense noncoding RNA in the INK4 locus (ANRIL) were found to affect cell inflammation,Nevertheless, the potential genes related to the inflammatory response regulated by ANRIL remain unclear. In this study, we investigated the potential function of ANRIL in regulating expression and alternative splicing. ANRIL-regulated human umbilical vein endothelial (HUVEC) cell transcriptome achieved by high-throughput RNA sequencing(RNA-seq) was obtained to investigate the potential role of ANRIL. Lipofectamine 2000 was used for plasmid transfection. The gene expression profile and alternative splicing pattern of HUVEC overexpressed by ANRIL were analyzed by RNA-seq and compared with the control group. ANRIL overexpression (ANRIL-OE) widely affects the transcription levels of genes related to inflammatory response, NF-κB pathway, type I interferon-mediated signal transduction pathway, and innate immune response. ANRIL extensively regulates the alternative splicing of hundreds of genes through functions such as gene expression, translation, DNA repair, RNA processing, and NF-κB pathway. Many of these genes have an indispensable role in the inflammatory response. ANRIL regulated inflammatory response may be achieved by regulating alternating splicing and potential transcription, which broadens the understanding of ANRIL-mediated gene regulation mechanisms and clarifies the role of ANRIL in mediating inflammatory response mechanisms.
2023-01-11 | GSE197115 | GEO
Project description:Background: Hyperglycemia-induced transcriptional alterations lead to aberrant synthesis of a large number of pathogenetic molecules leading to functional and structural damage to multiple end organs including the kidneys. Diabetic nephropathy (DN) remains a major cause of end stage renal disease. Multiple epigenetic mechanisms, including alteration of long non-coding RNAs (lncRNAs) may play a significant role mediating the cellular transcriptional activities. We have previously shown that lncRNA ANRIL may mediate diabetes associated molecular, functional and structural abnormalities in DN. Here we explored downstream mechanisms of ANRIL alteration in DN. Methods: We used renal cortical tissues from ANRIL knockout (KO) mice and wild type (WT) mice, with or without streptozotocin (STZ) induced diabetes for RNA sequencing. The differentially expressed genes were identified using edgeR and DESeq2 computational methods. KEGG and Reactome pathway analyses and network analyses using STRING and IPA were subsequently performed. Results: Diabetic animals showed hyperglycemia, reduced body weight gain, polyuria and increased urinary albumin. Both albuminuria and polyuria were corrected in the KO diabetic mice. RNA analyses showed Diabetes induced alterations of a large number of transcripts in the wild type (WT) animals. ANRIL knockout (KO) prevented a large number of such alterations. The altered transcripts include metabolic pathways, apoptosis, extracellular matrix protein synthesis and degradation, NFKB related pathways, AGE-RAGE interaction pathways etc. ANRIL KO prevented majority of these pathways. Conclusion: These findings suggest that as ANRIL regulates a large number of molecules of pathogenetic significance, it may potentially be a drug target for DN and other chronic diabetic complications.
2022-03-06 | GSE197699 | GEO
Project description:Redondoviridae is a recently identified family of DNA viruses associated with periodontitis. Circular RNAs (circRNAs) emerged as a novel endogenous, conserved noncoding RNAs, which contributed to the virus related immune‐inflammatory response. However, the characteristics and function of circRNAs in Redondoviridae related periodontal inflammation are not yet understood. The present study aimed to analyze the expression profiles of circRNAs in gingival tissues in periodontitis patients with and without Redondoviridae-infection and healthy controls using high-throughput RNA sequencing combined with experimental validation. Out of 17819 circRNAs, 175 circRNAs were dysregulated. Functional annotation and enrichment analysis of the differential circRNAs host genes demonstrated the potential alteration in the molecular and cellular components and metabolism in individuals suffering from periodontitis with Redondoviridae infection. Moreover, “axon guidance” (PATH:04360), “lysine biosynthesis” (PATH:00300) and “vascular endothelial growth factor signaling pathways” (PATH:04370) were significantly enriched in Redondoviridae infected gingivitis tissues. Furthermore, the key circRNAs (circCOL1A1, circAASS, circPTK2, circATP2B4, circDOCK1, circTTBK2, and circMCTP2) associated with the pathobiology of Redondoviridae related periodontitis were revealed by constructing circRNA-miRNA-mRNA networks. The bioinformatic analyses demonstrated that several abnormal expression circRNAs may contribute to the etiopathogenesis and development of Redondoviridae-related periodontitis. The findings of the present study have enhanced the current understanding of the mechanism of Redondoviridae-related periodontitis process and provide an insight into further applications for diagnostic markers and therapeutic uses.
2024-11-17 | GSE189022 | GEO
Project description:We performed Chromatin Isolation by RNA Purification (ChIRP-seq) of the lncRNA ANRIL in HEK293 cell line. We identified 3227 genomic regions to be contacted by ANRIL.
2021-05-26 | GSE162221 | GEO