Differentially expressed Transcribed ultraconserved regions (T-UCRs) in Crohn's disease (CD) comparing to normal controls (NC)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE83982 | GEO | 2016/07/05
SECONDARY ACCESSION(S): PRJNA327742
REPOSITORIES: GEO
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Project description:To date, 481 transcribed ultraconserved regions (T-UCRs) have been discovered in human genome. We aimed to investigate their characteristics in Crohnâs disease (CD) with conparison to healthy normal controls, to reveal differentially expressed T-UCRs. 3 CD patients and 3 NC volunteers were recruited in this study. With colonoscopy, colon mocosa pinch biopsy samles were got at inflammed site in CD patients and normal sites in NC volunteers respectively.
2016-07-05 | E-GEOD-83982 | biostudies-arrayexpress
Project description:Ultraconserved regions (UCRs) are segments of the human genome located in both intragenic and intergenic regions that are highly conserved in orthologous regions of the human, rat, and mouse genomes. Their transcriptional products, called T-UCRs, compose a new category of long noncoding RNA (lncRNAs). Most importantly, recent data suggests that T-UCRs are altered at the transcriptional level in human tumorigenesis and the aberrant T-UCRs expression profiles can be used to differentiate human cancer types. MicroRNAs and other types of non-codingRNAs have been shown to greatly contribute at biological function of cancer and are increasingly being used to help prognosticate patients with bladder cancer, this is not yet the case for T-UCRs. The presence and the roles for T-UCRs across different species is largely unknown rendering their investigation particularly important in our understanding the biology of cancer. Using genome-wide profiling, we identified 293 T-UCRs that were dysregulated in bladder tumor (n = 24) but not normal bladder tissues (n = 17) samples. The greatest change in expression was for the ultraconserved element 8 (uc.8+), whose expression significantly increased (6.7 fold; P = 0.001) in bladder cancer tissues. Dysregulated expression was validated for several T-UCRs in 60 patients and 16 healthy donors. We found that T-UCR 8+ acts as a natural decoy RNA for miR-596 in patients and bladder cancer cells. As a result, expression of matrix metallopeptidase 9, a direct target of this microRNA, was upregulated, thereby promoting cancer cell growth, migration, and invasion. We also observed that mir-596 mediated a network of interactions among uc.8+, uc.339+, uc.195+, and uc.388+, which appeared to be dysregulated in bladder tumors. Transcribed ultraconserved ncRNAs provide an evolutionarily-conserved regulatory layer that modulates miRNA levels, and opens up the possibility for the development of useful markers for diagnosis and prognosis, as well as for the development of new RNA-based cancer therapies.
2016-03-23 | GSE68594 | GEO
Project description:The transcribed ultraconserved regions (T-UCRs) are a family of long non-coding RNAs implicated in human carcinogenesis. The mechanism of action of T-UCRs and the factors regulating their expression in human cancers are poorly understood. In this study we show that high expression of uc.339 correlates with lower survival in 204 non-small cell lung cancer (NSCLC) patients. We also show that uc.339 found up-regulated in archival NSCLC samples, functions as a decoy for miR-339-3p, -663-3p and -95-5p. As a result, Cyclin E2, a direct target of these microRNAs is up-regulated, promoting cancer growth and migration. We provide evidence from cell lines and primary samples suggesting that TP53 directly regulates uc.339. Our results support a key role for uc.339 in lung cancer.
2015-07-07 | GSE70540 | GEO
Project description:In this study, we identified the dysregulated ultraconserved regions (UCRs) in Non-small-Cell Lung Cancer patients. We measured the expression profile of UCRs in 18 paired frozen tumor and adjacent non-tumor lung, by microarray analysis. This analysis is performed to identify the most significant dysregulated T-UCRs in tumor compared to the near non-cancerous lung tissue.
2021-12-07 | E-MTAB-11010 | biostudies-arrayexpress
Project description:The transcribed ultraconserved regions (T-UCRs) are a family of long non-coding RNAs implicated in human carcinogenesis. The mechanism of action of T-UCRs and the factors regulating their expression in human cancers are poorly understood. In this study we show that high expression of uc.339 correlates with lower survival in 204 non-small cell lung cancer (NSCLC) patients. We also show that uc.339 found up-regulated in archival NSCLC samples, functions as a decoy for miR-339-3p, -663-3p and -95-5p. As a result, Cyclin E2, a direct target of these microRNAs is up-regulated, promoting cancer growth and migration. We provide evidence from cell lines and primary samples suggesting that TP53 directly regulates uc.339. Our results support a key role for uc.339 in lung cancer. 4 experimental groups in triplicate (total: 12 samples). A339= A549 infected with a lentivirus over-expressing uc.339; AE= A549 infected with an empty lentivirus (control of A339); L339= LoVo infected with a lentivirus over-expressing uc.330; LE= LoVo infected with an empty lentivirus (control of L339). 1-2-3 refer to each experiment.
2015-07-07 | E-GEOD-70540 | biostudies-arrayexpress
Project description:A critical question in molecular oncology is how extensive is the involvement of non-codingRNAs (ncRNAs) in human tumorigenesis. Herein, we report that a large fraction of genomic ultraconserved regions (UCRs) are encoding a particular set of ncRNAs and are altered in human cancers. We show that UCRs are frequently located at fragile sites and genomic regions involved in cancers, and that genome-wide UCRs profiling reveals distinct signatures in human leukemias and carcinomas. We proved that the inhibition of an overexpressed UCR induces apoptosis in colon cancer cells, and we identified UCRs whose expression may be regulated by miRNAs abnormally expressed in human chronic lymphocytic leukemia (CLL). Our findings argue that non-coding genes are involved in tumorigenesis at a greater extent as thought before and offer the perspective of identification of signatures associated with diagnosis, prognosis and response to treatment composed by various categories of ncRNA genes.
2007-12-01 | E-TABM-184 | biostudies-arrayexpress
Project description:We investigate the role of a long ncRNA transcribed from an ultraconserved region (T-UCR) in the control of post-transcriptional pri-miRNA processing. The regulation is based on complementarity between the lower stem region in pri-miR-195 transcript and the ultraconserved sequence in Uc.283+A, which prevents pri-miRNA cleavage by Drosha. Mutation of the site in either RNA molecule uncouples regulation in vivo and in vitro. We propose a model in which lower-stem strand invasion by Uc.283+A impairs microprocessor recognition and efficient pri-miRNA cropping. In this work, we characterize a new role for Uc.283+A as a direct interactor and regulator of pri-miRNA-195 maturation at the level of Drosha processing. We combine cellular assays with in vitro biochemical analyses to reveal the first case of RNA-directed downregulation of miRNA biogenesis by a T-UCR
2014-05-01 | GSE56841 | GEO
Project description:We investigate the role of a long ncRNA transcribed from an ultraconserved region (T-UCR) in the control of post-transcriptional pri-miRNA processing. The regulation is based on complementarity between the lower stem region in pri-miR-195 transcript and the ultraconserved sequence in Uc.283+A, which prevents pri-miRNA cleavage by Drosha. Mutation of the site in either RNA molecule uncouples regulation in vivo and in vitro. We propose a model in which lower-stem strand invasion by Uc.283+A impairs microprocessor recognition and efficient pri-miRNA cropping. In this work, we characterize a new role for Uc.283+A as a direct interactor and regulator of pri-miRNA-195 maturation at the level of Drosha processing. We combine cellular assays with in vitro biochemical analyses to reveal the first case of RNA-directed downregulation of miRNA biogenesis by a T-UCR In the study presented here, a colorrectal cancer cell line (HCT-116) was transiently transfected with Uc.283+A in order to identify putative miRNA targets for Uc.283+A. Variant 1 represents a SNP variant (8x(T) repeat in the sequence). Variant 2 represents a SNP variant (9x(T) repeat in the sequence).
2014-05-01 | E-GEOD-56841 | biostudies-arrayexpress
Project description:Non-coding ultraconserved regions showing hundreds of consecutive bases of perfect evolutionary sequence conservation across mammalian genomes have intrigued biologists in the decade since they were first described. While many of these sequences are known to represent distant-acting enhancers, initial deletion studies in mice showed that their loss had no obvious impact on viability or fertility. To explore the discrepancy between extraordinary evolutionary constraint and an apparent lack of phenotypes when deleted in vivo, we used genome editing to create an expanded series of knockout mice lacking individual or combinations of ultraconserved brain enhancers near the essential neuronal transcription factor Arx. While the loss of any single or pair of ultraconserved enhancers resulted in viable and fertile mice, detailed phenotyping revealed neurological or growth abnormalities in nearly all cases, including substantial alterations of neuron populations and abnormalities of the dentate gyrus. Our results demonstrate the functional importance of ultraconserved enhancers and highlight that extreme sequence conservation may result from evolutionary selection against fitness deficits that appear subtle in a laboratory setting.
2018-01-17 | GSE100384 | GEO
Project description:Analysis of the transcriptional changes in the forebrain resulting from the loss of ultraconserved enhancers near Arx gene.
2018-01-17 | GSE97321 | GEO