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Ling Zhou, De-Yu Xu, Wen-Gang Sha, Lei Shen, Guo-Yuan Lu
BACKGROUND: Tubular injury is considered as a crucial pathological feature of diabetic nephropathy. LncRNA MALAT1 is involved in diabetic complications. Hence the role of MALAT1 in high glucose-induced renal tubular epithelial cells (HK-2) injury deserves investigation. METHODS: The diabetic mice model was established with streptozotocin (STZ) injection. The expression of NEAT1, SIRT1, and Foxo1 mRNA and protein was determined with qRT-PCR and western blot, respectively...
June 18, 2018: Biochemical and Biophysical Research Communications
Stephano Spano Mello, Laura Donatella Attardi
Although the p53 transcription factor has a well-established role in tumor suppression, little is known about how the non-coding targets of p53 mediate its tumor suppression function. Analysis of ncRNAs regulated by p53 revealed Neat1 as a direct p53 target gene. Neat1 has physiological roles in the development and differentiation of the mammary gland and corpus luteum, but its roles in cancer have been conflicting. To unequivocally understand Neat1 function in cancer, we used Neat1 null mice. Interestingly, we found that Neat1 deficiency promotes transformation both in oncogene-expressing fibroblasts and in a mouse model for pancreatic cancer...
June 12, 2018: Cell Cycle
Xin Li, Xianteng Wang, Wanlu Song, Hui Xu, Rongyao Huang, Yuting Wang, Wenwei Zhao, Zhengtao Xiao, Xuerui Yang
The long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) has been shown to regulate multiple cancer-related cellular activities including cell proliferation, apoptosis, and migration. In this study, we confirm that repression of NEAT1 induces DNA damage, disturbs the cell cycle, and arrests the proliferation of prostate cancer cells. By taking advantage of the prostate cancer tumor transcriptome profiles from The Cancer Genome Atlas (TCGA), our data-mining pipeline identified a series of transcription factors (TF) whose regulatory activities on target genes depended on the level of NEAT1...
June 5, 2018: Cancer Research
Li Qi, Fang Liu, Feng Zhang, Shuai Zhang, LiYan Lv, Yi Bi, Yan Yu
Non-small cell lung cancer (NSCLC) accounts for >80% of diagnosed cases of lung cancer worldwide. Although multiple genes are altered in NSCLC, the precise mechanism of NSCLC requires further investigation. Nuclear paraspeckle assembly transcript (NEAT)1 is one of the long non-coding RNAs implicated in multiple types of cancer regulation. However, the role of NEAT1 in NSCLC is poorly understood. In this study, we investigated the function of NEAT1 in NSCLC and its related molecular mechanism. We demonstrated via real-time polymerase chain reaction that NEAT1 was significantly increased in NSCLC tissues and cell lines, suggesting a potential role of NEAT1 in NSCLC...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Tatyana A Shelkovnikova, Michail S Kukharsky, Haiyan An, Pasquale Dimasi, Svetlana Alexeeva, Osman Shabir, Paul R Heath, Vladimir L Buchman
BACKGROUND: Paraspeckles are subnuclear bodies assembled on a long non-coding RNA (lncRNA) NEAT1. Their enhanced formation in spinal neurons of sporadic amyotrophic lateral sclerosis (ALS) patients has been reported but underlying mechanisms are unknown. The majority of ALS cases are characterized by TDP-43 proteinopathy. In current study we aimed to establish whether and how TDP-43 pathology may augment paraspeckle assembly. METHODS: Paraspeckle formation in human samples was analysed by RNA-FISH and laser capture microdissection followed by qRT-PCR...
June 1, 2018: Molecular Neurodegeneration
Jianfei Tu, Zhongwei Zhao, Min Xu, Xiaojie Lu, Liu Chang, Jiansong Ji
Increasing evidence has shown that the lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) play important roles in cell proliferation, migration, and invasion in various tumors. In our current study, we concentrated on the biological mechanisms of NEAT1 in hepatocellular carcinoma (HCC) development. It was found that NEAT1 was significantly increased in human HCC cell lines including Hep3B, LM3, MHCC97L, SK-hep1, and HepG2 cells compared to the normal human liver cell line LO2. Meanwhile, we observed that hsa-miR-139-5p was greatly decreased in HCC cells, which suggested a negative correlation between NEAT1 and hsa-mir-139-5p...
May 24, 2018: Journal of Cellular Physiology
Yangcheng Liu, Yong Wang, Xinming Fu, Zhi Lu
Long non-coding RNAs (lncRNAs) are extensively involved in various malignant tumors including ovarian cancer (OC). In the present study, we focused on the expression and function of nuclear enriched abundant transcript 1 (NEAT1) work on ovarian cancer cells' metastasis. We demonstrated that NEAT1 was up-regulated in OC tissue specimens and cell lines. Also, we revealed that depression of NEAT1 inhibited OC cells' metastasis and the expression of Rho associated coiled-coil containing protein kinase 1 (ROCK1) which was a metastasis-related gene...
May 23, 2018: Cancer Science
Wu Zhou, Xing Chen, Qinghua Hu, Xuliang Chen, Yingji Chen, Lingjin Huang
BACKGROUND: Lung cancer remains the top contributor to cancer-related mortality worldwide. Long non-coding RNAs (lncRNAs) have been reported to participate in normal development and tumorigenesis. LncRNA nuclear enriched abundant transcript 1 (NEAT1) is highly expressed in lung cancer and promotes lung cancer cell proliferation and migration. However, the upstream regulatory mechanism still needs investigation. METHODS: In the present study, we investigated the upstream regulators and mechanisms of NEAT1 expression disorders...
May 22, 2018: BMC Cancer
Xirui Liu, Yingjian Liang, Ruipeng Song, Guangchao Yang, Jihua Han, Yaliang Lan, Shangha Pan, Mingxi Zhu, Yao Liu, Yan Wang, Fanzheng Meng, Yifeng Cui, Jiabei Wang, Bo Zhang, Xuan Song, Zhaoyang Lu, Tongsen Zheng, Lianxin Liu
BACKGROUND: Abnormal metabolism, including abnormal lipid metabolism, is a hallmark of cancer cells. Some studies have demonstrated that the lipogenic pathway might promote the development of hepatocellular carcinoma (HCC). However, the role of the lipolytic pathway in HCC has not been elucidated. METHODS: We compared levels of adipose triglyceride lipase (ATGL) in human HCC and healthy liver tissues by real time PCR, western blot and immunohistochemistry. We measured diacylglycerol(DAG) and free fatty acid (FFA) levels in HCC cells driven by the NEAT1-ATGL axis and in HCC tissues...
May 15, 2018: Molecular Cancer
Yi Chen, Jialing Qiu, Bin Chen, Youping Lin, Yulan Chen, Guojin Xie, Junming Qiu, Huasheng Tong, Dongxin Jiang
This study aimed to explore the role of long non-coding RNA NEAT1 in sepsis-induced acute kidney injury (AKI). The expression levels of NEAT1 in sepsis-induced AKI patients were detected. The rat mesangial cells (RMCs) were treated with lipopolysaccharide (LPS) to induce cell injury. Then, the effects of NEAT1 suppression on the cell viability, apoptosis, cytokines expression, and oxidative stress in the LPS-stimulated RMCs were tested. The regulatory miRNA of NEAT1, as well as the target genes of this miRNA, were investigated...
June 2018: International Immunopharmacology
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...
May 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 the loss of dopaminergic neurons in the substantia nigra and is expected to increase the economic burden on patients' families and societies. NEAT1, a long non-coding 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...
June 3, 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...
April 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...
April 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
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