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Pietro Carotenuto, Matteo Fassan, Rosantony Pandolfo, Andrea Lampis, Caterina Vicentini, Luciano Cascione, Viola Paulus-Hock, Luke Boulter, Rachel Guest, Luca Quagliata, Jens Claus Hahne, Rachel Ridgway, Tam Jamieson, Dimitris Athineos, Angelo Veronese, Rosa Visone, Claudio Murgia, Giulia Ferrari, Vincenza Guzzardo, Thomas Ronald Jeffry Evans, Martin MacLeod, Gui Ji Feng, Trevor Dale, Massimo Negrini, Stuart J Forbes, Luigi Terracciano, Aldo Scarpa, Tushar Patel, Nicola Valeri, Paul Workman, Owen Sansom, Chiara Braconi
OBJECTIVE: Transcribed-ultraconserved regions (T-UCR) are long non-coding RNAs which are conserved across species and are involved in carcinogenesis. We studied T-UCRs downstream of the Wnt/β-catenin pathway in liver cancer. DESIGN: Hypomorphic Apc mice (Apcfl/fl) and thiocetamide (TAA)-treated rats developed Wnt/β-catenin dependent hepatocarcinoma (HCC) and cholangiocarcinoma (CCA), respectively. T-UCR expression was assessed by microarray, real-time PCR and in situ hybridisation...
September 12, 2016: Gut
Bao-Chun Jiang, Tian Yang, Li-Na He, Yuan-Xiang Tao, Yong-Jing Gao
Spinal cord plays an important role in the transmission and modulation of nociceptive information. Global changes in gene expression in the spinal cord contribute to the induction and maintenance of neuropathic pain. Transcribed Ultraconserved Regions (T-UCRs), a novel class of long noncoding RNAs, can regulate gene expression at both transcriptional and post-transcriptional levels and are related to many human diseases such as cancer, Alzheimer's disease, and heart diseases. In this study, we screened abnormal T-UCRs expression in the spinal cord under spinal nerve ligation (SNL)-induced neuropathic pain condition...
2016: Translational Perioperative and Pain Medicine
Alberto Marini, Anna Maria Lena, Emanuele Panatta, Cristina Ivan, Leng Han, Han Liang, Margherita Annicchiarico-Petruzzelli, Nicola Di Daniele, George A Calin, Eleonora Candi, Gerry Melino
Transcribed-ultraconserved regions (T-UCRs) are long non-coding RNAs (lncRNA) encoded by a subset of long ultraconserved stretches in the human genome. Recent studies revealed that the expression of several T-UCRs is altered in cancer and growing evidences underline the importance of T-UCRs in oncogenesis, offering also potential new strategies for diagnosis and prognosis. We found that overexpression of one specific T-UCRs named uc.63 is associated with bad outcome in luminal A subtype of breast cancer patients...
July 13, 2016: Oncotarget
Jinmai Jiang, Ana Clara P Azevedo-Pouly, Roxana S Redis, Eun Joo Lee, Yuriy Gusev, David Allard, Dhruvitkumar S Sutaria, Mohamed Badawi, Ola A Elgamal, Megan R Lerner, Daniel J Brackett, George A Calin, Thomas D Schmittgen
Transcribed ultraconserved regions (T-UCRs) are a class of non-coding RNAs with 100% sequence conservation among human, rat and mouse genomes. T-UCRs are differentially expressed in several cancers, however their expression in pancreatic adenocarcinoma (PDAC) has not been studied. We used a qPCR array to profile all 481 T-UCRs in pancreatic cancer specimens, pancreatic cancer cell lines, during experimental pancreatic desmoplasia and in the pancreases of P48Cre/wt; KrasLSL-G12D/wt mice. Fourteen, 57 and 29% of the detectable T-UCRs were differentially expressed in the cell lines, human tumors and transgenic mouse pancreases, respectively...
June 23, 2016: Oncotarget
Michele Olivieri, Matteo Ferro, Sara Terreri, Montano Durso, Alessandra Romanelli, Concetta Avitabile, Ottavio De Cobelli, Anna Messere, Dario Bruzzese, Ivan Vannini, Luciana Marinelli, Ettore Novellino, Wei Zhang, Mariarosaria Incoronato, Gennaro Ilardi, Stefania Staibano, Laura Marra, Renato Franco, Sisto Perdonà, Daniela Terracciano, Bogdan Czerniak, Giovanna L Liguori, Vincenza Colonna, Muller Fabbri, Ferdinando Febbraio, George A Calin, Amelia Cimmino
Ultraconserved regions (UCRs) have been shown to originate non-coding RNA transcripts (T-UCRs) that have different expression profiles and play functional roles in the pathophysiology of multiple cancers. The relevance of these functions to the pathogenesis of bladder cancer (BlCa) is speculative. To elucidate this relevance, we first used genome-wide profiling to evaluate the expression of T-UCRs in BlCa tissues. Analysis of two datasets comprising normal bladder tissues and BlCa specimens with a custom T-UCR microarray identified ultraconserved RNA (uc...
April 12, 2016: Oncotarget
Hua Lin, Weiguo Sui, Qiupei Tan, Jiejing Chen, Yue Zhang, Minglin Ou, Wen Xue, Fengyan Li, Cuihui Cao, Yufeng Sun, Yong Dai
Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease which affects different organs and systems that, has a complex genetic inheritance, and is affected by both epigenetic and environmental risk factors. Previous studies on SLE have lacked the statistical power and genetic resolution to fully determine the influence of major histocompatibility complex (MHC) on SLE. In this study, in order to determine this influence, a total of 15 patients with SLE and 15 healthy controls were enrolled...
January 2016: International Journal of Molecular Medicine
Aruo Nan, Xinke Zhou, Lijian Chen, Meiling Liu, Nan Zhang, Li Zhang, Yuanwei Luo, Zhenzhong Liu, Lijun Dai, Yiguo Jiang
As a common toxic metal, lead has significant neurotoxicity to brain development. Long non-coding RNAs (lncRNAs) function in multiple biological processes. However, whether lncRNAs are involved in lead-induced neurotoxicity remains unclear. Uc.173 is a lncRNA from a transcribed ultra-conservative region (T-UCR) of human, mouse and rat genomes. We established a lead-induced nerve injury mouse model. It showed the levels of Uc.173 decreased significantly in hippocampus tissue and serum of the model. We further tested the expression of Uc...
January 5, 2016: Oncotarget
K Goto, S Ishikawa, R Honma, K Tanimoto, N Sakamoto, K Sentani, N Oue, J Teishima, A Matsubara, W Yasui
The transcribed-ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs, which are absolutely conserved (100%) between the orthologous regions of the human, rat and mouse genomes. Previous studies have described that several T-UCRs show differential expressions in cancers and might be involved in cancer development. We investigated the transcriptional levels of representative 26 T-UCRs and determined the regions that were differently expressed in prostate cancer (PCa) and gastric cancer (GC). A quantitative reverse transcription-polymerase chain reaction analysis revealed the downregulation of Uc...
July 7, 2016: Oncogene
Julia Liz, Manel Esteller
Most diseases, including human cancer, are frequently associated with an altered transcription pattern. The alteration of the transcriptome is not restricted to the production of aberrant levels of protein-coding RNAs, but also refers to the dysregulation of the expression of the multiple noncoding members that comprise the human genome. Unexpectedly, recent RNA-seq data of the human transcriptome have revealed that less than 2% of the genome encodes protein-coding transcripts, even though the vast majority of the genome is actively transcribed into non-coding RNAs (ncRNAs) under different conditions...
January 2016: Biochimica et Biophysica Acta
Salvatore Alaimo, Rosalba Giugno, Alfredo Pulvirenti
MOTIVATION: Over the past few years, experimental evidence has highlighted the role of microRNAs to human diseases. miRNAs are critical for the regulation of cellular processes, and, therefore, their aberration can be among the triggering causes of pathological phenomena. They are just one member of the large class of non-coding RNAs, which include transcribed ultra-conserved regions (T-UCRs), small nucleolar RNAs (snoRNAs), PIWI-interacting RNAs (piRNAs), large intergenic non-coding RNAs (lincRNAs) and, the heterogeneous group of long non-coding RNAs (lncRNAs)...
2014: Frontiers in Bioengineering and Biotechnology
Matteo Fassan, Luigi Dall'Olmo, Marco Galasso, Chiara Braconi, Marco Pizzi, Stefano Realdon, Stefano Volinia, Nicola Valeri, Pierluigi Gasparini, Raffaele Baffa, Rhonda F Souza, Caterina Vicentini, Edoardo D'Angelo, Jan Bornschein, Gerard J Nuovo, Giovanni Zaninotto, Carlo M Croce, Massimo Rugge
Barrett's esophagus (BE) involves a metaplastic replacement of native esophageal squamous epithelium (Sq) by columnar-intestinalized mucosa, and it is the main risk factor for Barrett-related adenocarcinoma (BAc). Ultra-conserved regions (UCRs) are a class non-coding sequences that are conserved in humans, mice and rats. More than 90% of UCRs are transcribed (T-UCRs) in normal tissues, and are altered at transcriptional level in tumorigenesis. To identify the T-UCR profiles that are dysregulated in Barrett's mucosa transformation, microarray analysis was performed on a discovery set of 51 macro-dissected samples obtained from 14 long-segment BE patients...
August 30, 2014: Oncotarget
Suresh L Mehta, Ashutosh Dharap, Raghu Vemuganti
Emerging evidence indicates that 481 regions of the genome (>200 bp) that actively transcribe noncoding RNAs shows 100% homology between humans, rats and mice. These transcribed ultraconserved regions (T-UCRs) are thought to control the essential regulatory functions basic for life in rodents and mammals. Using microarray analysis, we presently show that 107 T-UCRs are actively expressed in adult rat cerebral cortex. They are grouped into intragenic (61) and intergenic (46) based on their genic location...
November 2014: Neurochemistry International
Jiang Chen Peng, Jun Shen, Zhi Hua Ran
Long non-coding RNAs (lncRNAs) are transcripts longer than ~200 nucleotides with little or no protein-coding capacity. Growing evidence shows that lncRNAs present important function in development and are associated with many human diseases such as cancers, Alzheimer disease, and heart diseases. Transcribed ultraconserved region (T-UCR) transcripts are a novel class of lncRNAs transcribed from ultraconserved regions (UCRs). UCRs are absolutely conserved (100%) between the orthologous regions of the human, rat, and mouse genomes...
December 2013: RNA Biology
Humberto J Ferreira, Holger Heyn, Xavier Garcia del Muro, August Vidal, Sara Larriba, Clara Muñoz, Alberto Villanueva, Manel Esteller
Although most cancer research has focused in mRNA, non-coding RNAs are also an essential player in tumorigenesis. In addition to the well-recognized microRNAs, recent studies have also shown that epigenetic silencing by CpG island hypermethylation of other classes of non-coding RNAs, such as transcribed ultraconserved regions (T-UCRs) or small nucleolar RNAs (snoRNAs), also occur in human neoplasia. Herein we have studied the putative existence of epigenetic aberrations in the activity of PIWI proteins, an Argonaute family protein subclass, and the small regulatory PIWI-interacting RNAs (piRNAs) in testicular cancer, as the PIWI/piRNA pathway plays a critical role in male germline development...
January 2014: Epigenetics: Official Journal of the DNA Methylation Society
J Ferdin, N Nishida, X Wu, M S Nicoloso, M Y Shah, C Devlin, H Ling, M Shimizu, K Kumar, M A Cortez, M Ferracin, Y Bi, D Yang, B Czerniak, W Zhang, T D Schmittgen, M P Voorhoeve, M J Reginato, M Negrini, R V Davuluri, T Kunej, M Ivan, G A Calin
Recent data have linked hypoxia, a classic feature of the tumor microenvironment, to the function of specific microRNAs (miRNAs); however, whether hypoxia affects other types of noncoding transcripts is currently unknown. Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs). Interestingly, several hypoxia-upregulated T-UCRs, henceforth named 'hypoxia-induced noncoding ultraconserved transcripts' (HINCUTs), are also overexpressed in clinical samples from colon cancer patients...
December 2013: Cell Death and Differentiation
Karen M Watters, Kenneth Bryan, Niamh H Foley, Maria Meehan, Raymond L Stallings
BACKGROUND: Ultra-conserved regions (UCRs) are segments of the genome (≥ 200 bp) that exhibit 100% DNA sequence conservation between human, mouse and rat. Transcribed UCRs (T-UCRs) have been shown to be differentially expressed in cancers versus normal tissue, indicating a possible role in carcinogenesis. All-trans-retinoic acid (ATRA) causes some neuroblastoma (NB) cell lines to undergo differentiation and leads to a significant decrease in the oncogenic transcription factor MYCN. Here, we examine the impact of ATRA treatment on T-UCR expression and investigate the biological significance of these changes...
2013: BMC Cancer
Jochen Buechner, Christer Einvik
Neuroblastoma is a pediatric tumor of the sympathetic nervous system. Amplification and overexpression of the MYCN proto-oncogene occurs in approximately 20% of neuroblastomas and is associated with advanced stage disease, rapid tumor progression, and poor prognosis. MYCN encodes the transcriptional regulator N-myc, which has been shown to both up- and downregulate many target genes involved in cell cycle, DNA damage, differentiation, and apoptosis in neuroblastoma. During the last years, it has become clear that N-myc also modulates the expression of several classes of noncoding RNAs, in particular microRNAs...
October 2012: Molecular Cancer Research: MCR
Humberto J Ferreira, Holger Heyn, Catia Moutinho, Manel Esteller
Much effort in cancer research has focused on the tiny part of our genome that codes for mRNA. However, it has recently been recognized that microRNAs also contribute decisively to tumorigenesis. Studies have also shown that epigenetic silencing by CpG island hypermethylation of microRNAs with tumor suppressor activities is a common feature of human cancer. The importance of other classes of non-coding RNAs, such as long intergenic ncRNAs (lincRNAs) and transcribed ultraconserved regions (T-UCRs) as altered elements in neoplasia, is also gaining recognition...
June 2012: RNA Biology
J Sana, S Hankeova, M Svoboda, I Kiss, R Vyzula, O Slaby
OBJECTIVES: The development of colorectal cancer (CRC) is characterized by multiple genetic alterations. Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed. It has recently been proven in cancer systems that differentially expressed T-UCRs could alter the functional characteristics of malignant cells. Genome-wide profiling revealed that T-UCRs have distinct signatures in human leukemia and carcinoma...
2012: Oncology
Manel Esteller
The relevance of the non-coding genome to human disease has mainly been studied in the context of the widespread disruption of microRNA (miRNA) expression and function that is seen in human cancer. However, we are only beginning to understand the nature and extent of the involvement of non-coding RNAs (ncRNAs) in disease. Other ncRNAs, such as PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), transcribed ultraconserved regions (T-UCRs) and large intergenic non-coding RNAs (lincRNAs) are emerging as key elements of cellular homeostasis...
December 2011: Nature Reviews. Genetics
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