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Chromatin-associated LncRNA

Stephen Harrap
Genetic discovery in blood pressure is generally referenced in relation to protein-coding genes, despite the fact that genes less than 2% of the genome. Recent exploration of the DNA sequences between genes, once called "junk" DNA, has revealed a wealth of transcripts for RNA species that do not encode protein. These non-coding RNAs (ncRNAs) have emerged as dynamic managers of the business of the genome, able to coordinate the expression of genes in time and space to achieve the complexities of normal development and growth...
September 2016: Journal of Hypertension
Lei Liu, Xihe Zhao, Huawei Zou, Rubing Bai, Keyu Yang, Zhong Tian
Hypoxia-inducible factor (HIF) activates the transcription of genes involved in cancer progression. Recently, HIF was reported to regulate the transcription of non-coding RNAs. Here, we show that the transcription of a long non-coding RNA (lncRNA), Gastric Adenocarcinoma Associated, Positive CD44 Regulator, Long Intergenic Non-Coding RNA (GAPLINC), is directly activated by HIF-1α in gastric cancer (GC). GAPLINC was overexpressed in GC tissues and promoted tumor migration and invasive behavior. GAPLINC overexpression was associated with poor prognosis in GC patients...
2016: Frontiers in Physiology
Jessica J DeWitt, Nicole Grepo, Brent Wilkinson, Oleg V Evgrafov, James A Knowles, Daniel B Campbell
We previously identified the long noncoding RNA (lncRNA) MSNP1AS (moesin pseudogene 1, antisense) as a functional element revealed by genome wide significant association with autism spectrum disorder (ASD). MSNP1AS expression was increased in the postmortem cerebral cortex of individuals with ASD and particularly in individuals with the ASD-associated genetic markers on chromosome 5p14.1. Here, we mimicked the overexpression of MSNP1AS observed in postmortem ASD cerebral cortex in human neural progenitor cell lines to determine the impact on neurite complexity and gene expression...
2016: Genes
Li-Juan Ding, Yan Li, Shu-Dong Wang, Xin-Sen Wang, Fang Fang, Wei-Yao Wang, Peng Lv, Dong-Hai Zhao, Feng Wei, Ling Qi
Hepatocellular carcinoma (HCC) is the most common subtype of liver malignancy, and it is characterized by poor prognosis because of cancer stem cell (CSC)-mediated high postsurgical recurrence rates. Thus, targeting CSCs, or HCC cells with CSC-like properties, is an effective strategy for HCC therapy. Here, using long noncoding RNA (lncRNA) microarray analysis, we identified a novel lncRNA termed lncCAMTA1 that is increased in both liver CSCs and HCC. High lncCAMTA1 expression in HCC indicates poor clinical outcome...
2016: International Journal of Molecular Sciences
Alec N Sexton, Martin Machyna, Matthew D Simon
There are numerous recent cases where chromatin modifying complexes associate with long noncoding RNA (lncRNA), stoking interest in lncRNA genomic localization and associated proteins. Capture Hybridization Analysis of RNA Targets (CHART) uses complementary oligonucleotides to purify an RNA with its associated genomic DNA or proteins from formaldehyde cross-linked chromatin. Deep sequencing of the purified DNA fragments gives a comprehensive profile of the potential lncRNA biological targets in vivo. The combined identification of the genomic localization of RNA and its protein partners can directly inform hypotheses about RNA function, including recruitment of chromatin modifying complexes...
2016: Methods in Molecular Biology
Ming Sun, Fengqi Nie, Yunfei Wang, Zhihong Zhang, Jiakai Hou, Dandan He, Min Xie, Wei De, Zhaoxia Wang, Jun Wang
Long noncoding RNAs (lncRNA) have been implicated in human cancer but their mechanisms of action are mainly undocumented. In this study, we investigated lncRNA alterations that contribute to gastric cancer (GC) through an analysis of TCGA RNA sequencing data and other publicly available microarray data. Here we report the GC-associated lncRNA HOXA11-AS as a key regulator of GC development and progression. Patients with high HOXA11-AS expression had a shorter survival and poorer prognosis. In vitro and in vivo assays of HOXA11-AS alterations revealed a complex integrated phenotype affecting cell growth, migration, invasion and apoptosis...
September 20, 2016: Cancer Research
Stephen Harrap
Genetic discovery in blood pressure is generally referenced in relation to protein-coding genes, despite the fact that genes less than 2% of the genome. Recent exploration of the DNA sequences between genes, once called "junk" DNA, has revealed a wealth of transcripts for RNA species that do not encode protein. These non-coding RNAs (ncRNAs) have emerged as dynamic managers of the business of the genome, able to coordinate the expression of genes in time and space to achieve the complexities of normal development and growth...
September 2016: Journal of Hypertension
Ryan Ard, Robin C Allshire
Long non-coding RNA (lncRNA) transcription into a downstream promoter frequently results in transcriptional interference. However, the mechanism of this repression is not fully understood. We recently showed that drug tolerance in fission yeast Schizosaccharomyces pombe is controlled by lncRNA transcription upstream of the tgp1(+) permease gene. Here we demonstrate that transcriptional interference of tgp1(+) involves several transcription-coupled chromatin changes mediated by conserved elongation factors Set2, Clr6CII, Spt6 and FACT...
September 8, 2016: Nucleic Acids Research
Hong-Wei Ma, Min Xie, Ming Sun, Tian-Yu Chen, Rong-Rong Jin, Tian-Shi Ma, Qin-Nan Chen, Er-Bao Zhang, Xue-Zhi He, Wei De, Zhi-Hong Zhang
Gastric cancer (GC) is the third leading cause of cancer death due to its poor prognosis and limited treatment options. Evidence indicates that pseudogene-derived long noncoding RNAs (lncRNAs) may be important players in human cancer progression, including GC. In this paper, we report that a newly discovered pseudogene-derived lncRNA named DUXAP8, a 2107-bp RNA, was remarkably upregulated in GC. Additionally, a higher level of DUXAP8 expression in GC was significantly associated with greater tumor size, advanced clinical stage, and lymphatic metastasis...
August 5, 2016: Oncotarget
Sheena M Saayman, Amanda Ackley, Jon Burdach, Matthew Clemson, Dieter C Gruenert, Kiyoshi Tachikawa, Pad Chivukula, Marc S Weinberg, Kevin V Morris
Cystic fibrosis (CF) is a life-shortening genetic disease. The root cause of CF is heritable recessive mutations that affect the cystic fibrosis transmembrance conductance regulator (CFTR) gene and the subsequent expression and activity of encoded ion channels at the cell surface. We show that CFTR is regulated transcriptionally by the actions of a novel long noncoding RNA (lncRNA), designated as BGas, that emanates from intron 11 of the CFTR gene and is expressed in the antisense orientation relative to the protein coding sense strand...
August 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
Sergio Leone, Raffaella Santoro
Long noncoding RNA (lncRNA) are emerging as important regulators of diverse biological functions. Although mechanistic models are starting to emerge, it is also clear that the lncRNA field needs appropriate model systems in order to better elucidate the functions of lncRNA and their roles in both physiological and pathological conditions. The field of lncRNA is new, and the biochemical and genetic methods used to address function and mechanisms of lncRNA have only recently been developed or adapted from techniques used to investigate protein-coding genes...
August 2016: FEBS Letters
Lin Jiang, Wenchao Wang, Guoli Li, Canlin Sun, Zhenqin Ren, Haihui Sheng, Hengjun Gao, Chaofu Wang, Hong Yu
PURPOSE: Long noncoding RNAs (lncRNAs) play critical roles in diverse biological processes such as tumorigenesis and metastasis. Taurine upregulated gene 1 (TUG1) is a cancer-related lncRNA that is associated with chromatin-modifying complexes and plays an important role in gene regulation. In this study, we determined the expression patterns of TUG1 in esophageal squamous cell carcinoma (ESCC) and evaluated its clinical significance. METHODS: The expression level of TUG1 was examined in 218 pairs of ESCC and adjacent non-cancerous tissues by using quantitative real-time polymerase chain reaction...
August 2016: Cancer Chemotherapy and Pharmacology
Chunlai Li, Liuqing Yang, Chunru Lin
A large proportion of the control of gene expression in humans is mediated by noncoding elements in the genome. Long noncoding RNAs (lncRNAs) have emerged as a new class of pivotal regulatory components, orchestrating extensive cellular processes and connections. LncRNAs play various roles from chromatin modification to alternative splicing and post-transcriptional processing and are involved in almost all aspects of eukaryotic regulation. LncRNA-based mechanisms modulate cell fates during development, and their dysregulation underscores many human disorders, especially cancer, through chromosomal translocation, deletion, and nucleotide expansions...
July 2014: Molecular & Cellular Oncology
Simin Zhang, Guangzheng Zhong, Wang He, Hao Yu, Jian Huang, Tianxin Lin
PURPOSE: While lncRNAs (long noncoding RNAs) have been shown to have critical regulatory roles in cancer biology, the biological functions and prognostic values in nonmuscle invasive bladder cancer remain largely unknown. We identified a lncRNA termed lncRNA-UNMIBC (up-regulated in nonmuscle invasive bladder cancer) and evaluated its prognostic value in patients with primary nonmuscle invasive bladder cancer. MATERIALS AND METHODS: We analyzed the expression of lncRNA-UNMIBC in the tissues of 75 cases of primary nonmuscle invasive bladder cancer and adjacent normal mucosa by quantitative real-time polymerase chain reaction...
October 2016: Journal of Urology
Kohei Kumegawa, Reo Maruyama, Eiichiro Yamamoto, Masami Ashida, Hiroshi Kitajima, Akihiro Tsuyada, Takeshi Niinuma, Masahiro Kai, Hiro-O Yamano, Tamotsu Sugai, Takashi Tokino, Yasuhisa Shinomura, Kohzoh Imai, Hiromu Suzuki
Long noncoding RNAs (lncRNAs) have emerged as key components in multiple cellular processes, although their physiological and pathological functions are not fully understood. To identify cancer-related lncRNAs, we screened for those that are epigenetically silenced in colorectal cancer (CRC). Through a genome-wide analysis of histone modifications in CRC cells, we found that the transcription start sites (TSSs) of 1,027 lncRNA genes acquired trimethylation of histone H3 lysine 4 (H3K4me3) after DNA demethylation...
2016: Scientific Reports
Raquel Pérez-Palacios, Sofía Macías-Redondo, María Climent, Bruno Contreras-Moreira, Pedro Muniesa, Jon Schoorlemmer
BACKGROUND: Yin Yang 2 (YY2) is a zinc finger protein closely related to the well-characterized Yin Yang 1 (YY1). YY1 is a DNA-binding transcription factor, with defined functions in multiple developmental processes, such as implantation, cell differentiation, X inactivation, imprinting and organogenesis. Yy2 has been treated as a largely immaterial duplication of Yy1, as they share high homology in the Zinc Finger-region and similar if not identical in vitro binding sites. In contrast to these similarities, gene expression alterations in HeLa cells with attenuated levels of either Yy1 or Yy2 were to some extent gene-specific...
2016: PloS One
Florian Bohne, David Langer, Ursula Martiné, Claudia S Eider, Regina Cencic, Matthias Begemann, Miriam Elbracht, Luzie Bülow, Thomas Eggermann, Ulrich Zechner, Jerry Pelletier, Bernhard Ulrich Zabel, Thorsten Enklaar, Dirk Prawitt
BACKGROUND: Genomic imprinting evolved in a common ancestor to marsupials and eutherian mammals and ensured the transcription of developmentally important genes from defined parental alleles. The regulation of imprinted genes is often mediated by differentially methylated imprinting control regions (ICRs) that are bound by different proteins in an allele-specific manner, thus forming unique chromatin loops regulating enhancer-promoter interactions. Factors that maintain the allele-specific methylation therefore are essential for the proper transcriptional regulation of imprinted genes...
2016: Clinical Epigenetics
Emily K Meredith, Maggie M Balas, Karla Sindy, Krystal Haislop, Aaron M Johnson
The human long noncoding RNA (lncRNA) HOTAIR acts in trans to recruit the Polycomb repressive complex 2 (PRC2) to the HOXD gene cluster and to promote gene silencing during development. In breast cancers, overexpression of HOTAIR increases metastatic potential via the repression of many additional genes. It has remained unclear what factors determine HOTAIR-dependent PRC2 activity at specific genomic loci, particularly when high levels of HOTAIR result in aberrant gene silencing. To identify additional proteins that contribute to the specific action of HOTAIR, we performed a quantitative proteomic analysis of the HOTAIR interactome...
July 2016: RNA
Jing Liu, Xiangdong Sun, Hongcheng Zhu, Qin Qin, Xi Yang, Xinchen Sun
Esophageal carcinoma is one of the most lethal cancer types in the world, especially in some part of China. Esophageal squamous cell carcinoma is a major subtype, which has been shown to be associated with unhealthy diet habit, smoking, environmental carcinogens etc. The esophageal squamous cell carcinoma (ESCC) often progress slowly, however, it is often diagnosed at an advanced stage. Thus it is imperative to elucidate the molecular mechanisms involved in the initiation and progression of ESCC. Long noncoding RNAs (lncRNA) has emerged as a novel functional player transcribed from the genome...
March 31, 2016: Journal of Biochemistry
Chan Zhou, Samuel R York, Jennifer Y Chen, Joshua V Pondick, Daniel L Motola, Raymond T Chung, Alan C Mullen
BACKGROUND: Hepatic fibrosis is the underlying cause of cirrhosis and liver failure in nearly every form of chronic liver disease, and hepatic stellate cells (HSCs) are the primary cell type responsible for fibrosis. Long noncoding RNAs (lncRNAs) are increasingly recognized as regulators of development and disease; however, little is known about their expression in human HSCs and their function in hepatic fibrosis. METHODS: We performed RNA sequencing and ab initio assembly of RNA transcripts to define the lncRNAs expressed in human HSC myofibroblasts...
2016: Genome Medicine
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