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David C Wedge, Gunes Gundem, Thomas Mitchell, Dan J Woodcock, Inigo Martincorena, Mohammed Ghori, Jorge Zamora, Adam Butler, Hayley Whitaker, Zsofia Kote-Jarai, Ludmil B Alexandrov, Peter Van Loo, Charlie E Massie, Stefan Dentro, Anne Y Warren, Clare Verrill, Dan M Berney, Nening Dennis, Sue Merson, Steve Hawkins, William Howat, Yong-Jie Lu, Adam Lambert, Jonathan Kay, Barbara Kremeyer, Katalin Karaszi, Hayley Luxton, Niedzica Camacho, Luke Marsden, Sandra Edwards, Lucy Matthews, Valeria Bo, Daniel Leongamornlert, Stuart McLaren, Anthony Ng, Yongwei Yu, Hongwei Zhang, Tokhir Dadaev, Sarah Thomas, Douglas F Easton, Mahbubl Ahmed, Elizabeth Bancroft, Cyril Fisher, Naomi Livni, David Nicol, Simon Tavaré, Pelvender Gill, Christopher Greenman, Vincent Khoo, Nicholas Van As, Pardeep Kumar, Christopher Ogden, Declan Cahill, Alan Thompson, Erik Mayer, Edward Rowe, Tim Dudderidge, Vincent Gnanapragasam, Nimish C Shah, Keiran Raine, David Jones, Andrew Menzies, Lucy Stebbings, Jon Teague, Steven Hazell, Cathy Corbishley, Johann de Bono, Gerhardt Attard, William Isaacs, Tapio Visakorpi, Michael Fraser, Paul C Boutros, Robert G Bristow, Paul Workman, Chris Sander, Freddie C Hamdy, Andrew Futreal, Ultan McDermott, Bissan Al-Lazikani, Andrew G Lynch, G Steven Bova, Christopher S Foster, Daniel S Brewer, David E Neal, Colin S Cooper, Rosalind A Eeles
Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers...
April 16, 2018: Nature Genetics
Yasnee Beeharry, Gabrielle Goodrum, Christian J Imperiale, Martin Pelchat
The Hepatitis Delta Virus (HDV) relies mainly on host proteins for its replication. We previously identified that PSF and p54nrb associate with the HDV RNA genome during viral replication. Together with PSP1, these proteins are part of paraspeckles, which are subnuclear bodies nucleated by the long non-coding RNA NEAT1. In this work, we established the requirement for PSF, p54nrb and PSP1 in HDV replication using RNAi-mediated knockdown in HEK-293 cells replicating the HDV RNA genome. We determined that HDV replication induces the delocalization of PSP1 to cytoplasmic foci containing PABP and increases NEAT1 level causing an enlargement of NEAT1 foci...
April 16, 2018: Scientific Reports
Hua-Sheng Chiu, Sonal Somvanshi, Ektaben Patel, Ting-Wen Chen, Vivek P Singh, Barry Zorman, Sagar L Patil, Yinghong Pan, Sujash S Chatterjee, Anil K Sood, Preethi H Gunaratne, Pavel Sumazin
Long noncoding RNAs (lncRNAs) are commonly dysregulated in tumors, but only a handful are known to play pathophysiological roles in cancer. We inferred lncRNAs that dysregulate cancer pathways, oncogenes, and tumor suppressors (cancer genes) by modeling their effects on the activity of transcription factors, RNA-binding proteins, and microRNAs in 5,185 TCGA tumors and 1,019 ENCODE assays. Our predictions included hundreds of candidate onco- and tumor-suppressor lncRNAs (cancer lncRNAs) whose somatic alterations account for the dysregulation of dozens of cancer genes and pathways in each of 14 tumor contexts...
April 3, 2018: Cell Reports
Ying Liu, Zuneng Lu
Parkinson's disease (PD) is a result of loss dopaminergic neurons in the substantia nigra and is expected to increase the economic burden on patients' families and societies. NEAT1, a long noncoding RNA, is known as a cancer-related gene, however, the role of it in PD remains unclear. The aims of this study are to detect the NEAT1-mediated effects in PD and explore the mechanism of NEAT1 in PD. One group (n=6) of C57BL/6 model mice were intraperitoneal injected with 1-Methyl-4-phenyl-2, 3, 6-tetrahydropyridine (MPTP), while another group (n=6) was treated with saline and served as control...
March 25, 2018: Clinical and Experimental Pharmacology & Physiology
Fei Liu, Yong Tai, Jiqing Ma
The long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) was reported to be upregulated and be involved in oncogenic growth and drug resistance in nasopharyngeal carcinoma (NPC). However, the exact roles of NEAT1 and its underlying mechanisms in the drug resistance of NPC remain largely unclear. In this study, the expressions of NEAT1, let-72-5p and Rsf-1 mRNA were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effects of NEAT1 and let-72-5p on cell proliferation and cisplatin resistance of NPC cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and 5-ethynyl-20-deoxyuridine (EdU) assay...
March 22, 2018: Cancer Biology & Therapy
Hao Wang, Mingxia Zhang, Guoping Sun
This study aimed to elucidate the roles of long non-coding RNA Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) in gastric cancer. The expression of NEAT1 in gastric cancer tissues and cells was determined. NEAT1 was then overexpressed and suppressed in BGC-823 cells in vitro to further explore the effects of NEAT1 on cell proliferation, migration, and invasion. In addition, the regulatory relationship among NEAT1, miR-335-5p and Rho Associated Coiled-Coil Containing Protein Kinase 1 (ROCK1) was investigated...
March 5, 2018: Die Pharmazie
Zhi Ruan, Hui Ma, Jing Li, Huiyong Liu, Haoruo Jia, Feng Li
Intervertebral disc degeneration is a complex disease involving genetic and environmental factors and multiple cellular processes. The role and expression of the lncRNA NEAT1 were assessed in intervertebral disc degeneration. NEAT1 expression was assessed in degenerative and control nucleus pulposus using RT-PCR. Western blotting and RT-PCR were also used to investigate p53 and p21 levels in nucleus pulposus tissues. NEAT1 function in degenerative nucleus pulposus cells was assessed with gain- and loss-of-function experiments...
January 1, 2018: Experimental Biology and Medicine
Wei Sun, Xiabin Lan, Hao Zhang, Zhihong Wang, Wenwu Dong, Liang He, Ting Zhang, Ping Zhang, Jinhao Liu, Yuan Qin
Nuclear paraspeckle assembly transcript 1 (NEAT1), a long non-coding RNA (lncRNA), is a core structural component of paraspeckles and is essential for paraspeckle formation. NEAT1 comprises two different isoforms: NEAT1_1 (3.7 kb) and NEAT1_2 (23 kb). Recently, NEAT1 has been shown to have oncogenic roles and to facilitate tumorigenesis in various human cancers. However, the function of NEAT1 in papillary thyroid cancer (PTC) is not well understood. The relative expression levels of NEAT1_2, ATPase family AAA domain-containing protein 2 (ATAD2), and microRNA-106b-5p (miR-106b-5p) were assessed via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR)...
March 7, 2018: Cell Death & Disease
Gang Huang, Xin He, Xin-Li Wei
Long non‑coding RNAs (lncRNAs) have emerged as critical regulators of tumor progression. However, the function and mechanism of lncRNA NEAT1 in oral squamous cell carcinoma (OSCC) are unclear. In the present study, NEAT1 was significantly upregulated in OSCC cells and tissues. High expression of NEAT1 was correlated with advanced TNM stage and poor survival of patients. Using bioinformatics prediction and experimental analysis, we determined that NEAT1 could negatively regulate the expression of miR‑365...
February 26, 2018: Oncology Reports
Yan Zhang, Xin Li, Dianshuang Zhou, Hui Zhi, Peng Wang, Yue Gao, Maoni Guo, Ming Yue, Yanxia Wang, Weitao Shen, Shangwei Ning, Yixue Li, Xia Li
Differences in individual drug responses is an obstacle to progression in cancer treatment, and predicting responses would help to plan treatment. The accumulation of cancer molecular profiling and drug response data provides opportunities and challenges to identify novel molecular signatures and mechanisms of tumor responsiveness to drugs. This study evaluated drug responses with a competing endogenous RNA (ceRNA) system that depended on competition between diverse RNA species. We identified drug response-related ceRNAs (DRCEs) by combining the sequence and expression data of long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and messenger RNAs (mRNAs) and the survival data of cancer patients treated with drugs...
February 21, 2018: Molecular Oncology
Tetsutaro Hayashi, Haruka Ozaki, Yohei Sasagawa, Mana Umeda, Hiroki Danno, Itoshi Nikaido
Total RNA sequencing has been used to reveal poly(A) and non-poly(A) RNA expression, RNA processing and enhancer activity. To date, no method for full-length total RNA sequencing of single cells has been developed despite the potential of this technology for single-cell biology. Here we describe random displacement amplification sequencing (RamDA-seq), the first full-length total RNA-sequencing method for single cells. Compared with other methods, RamDA-seq shows high sensitivity to non-poly(A) RNA and near-complete full-length transcript coverage...
February 12, 2018: Nature Communications
Hengchuan Su, Hongkai Wang, Guohai Shi, Hailiang Zhang, Fukang Sun, Dingwei Ye
OBJECTIVE: In order to identify potential novel biomarkers of advanced clear cell renal cell carcinoma (ccRCC), we re-evaluated published long non-coding RNA (lncRNA) expression profiling data. MATERIALS AND METHODS: The lncRNA expression profiles in ccRCC microarray dataset GSE47352 were analyzed and an independent cohort of 61 clinical samples including 21 advanced and 40 localized ccRCC patients was used to confirm the most statistically significant lncRNAs by real time PCR...
January 13, 2018: European Journal of Surgical Oncology
Yong Li, Cai Cheng
Osteosarcoma (OS) is the most common histological form of primary bone cancer. Long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) functions as an oncogene in some cancers. However, the functional role of NEAT1 in OS metastasis remains elusive. In the present study, we found that NEAT1 expression was significantly increased in OS tissues and cell lines. Overexpression of NEAT1 in OS tissues was correlated with higher clinical stage, distant metastasis and poorer prognosis. Loss- and gain-of-function assays showed that NEAT1 positively regulated metastasis in vitro and in vivo ...
2018: American Journal of Cancer Research
Dongmei Han, Jianfeng Wang, Guanghui Cheng
LncRNAs have become a hot topic in various cancer-related researches. Radio-resistance is a great threat for cancer therapy. However, how lncRNAs affect the radio-resistance in cervical cancer is masked. As for our paper, it was discovered that NEAT1 was highly expressed in cervical cancer tissues and non-sensitive tissues as well as radio-resistant cell lines. And the overexpression of NEAT1 accelerated proliferation, while the knockdown of NEAT1 had the opposite result. The effect of NEAT1 on cell proliferation was dependent on the dose of ionizing radiation...
January 5, 2018: Oncotarget
Julien Bouckenheimer, Patricia Fauque, Charles-Henri Lecellier, Céline Bruno, Thérèse Commes, Jean-Marc Lemaître, John De Vos, Said Assou
Progress in assisted reproductive technologies strongly relies on understanding the regulation of the dialogue between oocyte and cumulus cells (CCs). Little is known about the role of long non-coding RNAs (lncRNAs) in the human cumulus-oocyte complex (COC). To this aim, publicly available RNA-sequencing data were analyzed to identify lncRNAs that were abundant in metaphase II (MII) oocytes (BCAR4, C3orf56, TUNAR, OOEP-AS1, CASC18, and LINC01118) and CCs (NEAT1, MALAT1, ANXA2P2, MEG3, IL6STP1, and VIM-AS1)...
February 2, 2018: Scientific Reports
Yizhu Lin, Brigitte F Schmidt, Marcel P Bruchez, C Joel McManus
Paraspeckles are nuclear bodies that regulate multiple aspects of gene expression. The long non-coding RNA (lncRNA) NEAT1 is essential for paraspeckle formation. NEAT1 has a highly ordered spatial organization within the paraspeckle, such that its 5' and 3' ends localize on the periphery of paraspeckle, while central sequences of NEAT1 are found within the paraspeckle core. As such, the structure of NEAT1 RNA may be important as a scaffold for the paraspeckle. In this study, we used SHAPE probing and computational analyses to investigate the secondary structure of human and mouse NEAT1...
January 31, 2018: Nucleic Acids Research
Shunheng Zhou, Lihong Wang, Qian Yang, Haizhou Liu, Qianqian Meng, Leiming Jiang, Shuyuan Wang, Wei Jiang
BACKGROUND: Breast cancer is one of the most common solid tumors in women involving multiple subtypes. However, the mechanism for subtypes of breast cancer is still complicated and unclear. Recently, several studies indicated that long non-coding RNAs (lncRNAs) could act as sponges to compete miRNAs with mRNAs, participating in various biological processes. METHODS: We concentrated on the competing interactions between lncRNAs and mRNAs in four subtypes of breast cancer (basal-like, HER2+, luminal A and luminal B), and analyzed the impacts of competing endogenous RNAs (ceRNAs) on each subtype systematically...
February 1, 2018: Breast Cancer Research and Treatment
Hai-Yang Tan, Changcheng Wang, Gao Liu, Xiang Zhou
Accumulating evidence has indicated that lncRNA NEAT1 exerts critical roles in cancers. So far, the detailed biological role and mechanisms of NEAT1 which are responsible for human gastric cancer (GC) is still largely unknown. Here, we observed that NEAT1 and STAT3 expression were significantly upregulated in human gastric cancer cells including BGC823, SGC-7901, AGS, MGC803 and MKN28 cells compared to normal gastric epithelial cells GES-1 while miR-506 was downregulated. We inhibited NEAT1 and observed that NEAT1 inhibition was able to repress the growth, migration and invasion of gastric cancer cells...
January 24, 2018: Journal of Cellular Biochemistry
Xing Jiang, Yong Zhou, Ai-Jun Sun, Jun-Li Xue
Breast cancer is a kind of common female cancers. Increasing evidence has exhibited that lncRNAs exert a crucial role in breast cancer. So far, the mechanism of lncRNAs in breast cancer is still not well established. In our current study, we focused on the biological role of lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in breast cancer. We observed that NEAT1 levels were significantly increased in human breast cancer cells including MCF-7, MDA-MB-453, MDA-MB-231and SKBR3 cells compared to normal mammary epithelial cells MCF-10A while miR-448 was decreased...
January 11, 2018: Journal of Cellular Physiology
Hong Zhang, Yuechang Cai, Li Zheng, Zhanlei Zhang, Xiaofeng Lin, Ningyi Jiang
PURPOSE: Considering the dilemma in papillary thyroid cancer treatment, this study intended to find solution in molecular respect. By probing into lncRNA-NEAT1/miR-129-5p/ KLK7 interaction, this study would provide new targets for future treatment. METHODS: Microarray analysis and R language package were applied to select possible lncRNA and miRNA. Luciferase reporter assay and RNA pull-down test were employed in the detection of target relationship between lncRNA and miRNA...
January 10, 2018: Journal of Cellular Physiology
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