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Tobias C Messemaker, Loubna Chadli, Guoshuai Cai, Varshna S Goelela, Maaike Boonstra, Annemarie L Dorjée, Stefan N Andersen, Harald M M Mikkers, Peter van 't Hof, Hailiang Mei, Oliver Distler, Harmen H M Draisma, Michael E Johnson, Nicole M Orzechowski, Robert W Simms, Rene E M Toes, Jamil Aarbiou, Tom W Huizinga, Michael L Whitfield, Jeroen DeGroot, Jeska de Vries-Bouwstra, Fina Kurreeman
Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and multiple organs of which the pathogenesis is poorly understood. Here we studied differentially expressed coding and non-coding genes in relation to SSc pathogenesis with a specific focus on antisense non-coding RNAs. Skin biopsy-derived RNAs from fourteen early SSc patients and six healthy individuals were sequenced with ion-torrent and analysed using DEseq2. Overall, 4901 genes with a fold change >1.5 and a false discovery rate < 5% were detected in patients versus controls...
November 24, 2017: Journal of Investigative Dermatology
Wen Wang, Zheng Zhao, Fan Yang, Haoyuan Wang, Fan Wu, Tingyu Liang, Xiaoyan Yan, Jiye Li, Qing Lan, Jiangfei Wang, Jizong Zhao
We investigated immune-related long non-coding RNAs (lncRNAs) that may be exploited as potential therapeutic targets in anaplastic gliomas. We obtained 572 lncRNAs and 317 immune genes from the Chinese Glioma Genome Atlas microarray and constructed immune-related lncRNAs co-expression networks to identify immune-related lncRNAs. Two additional datasets (GSE16011, REMBRANDT) were used for validation. Gene set enrichment analysis and principal component analysis were used for functional annotation. Immune-lncRNAs co-expression networks were constructed...
January 2018: Journal of Neuro-oncology
Brent Wilkinson, Jing Li, Marcelo P Coba
GTPase-activating proteins (GAPs) and guanine exchange factors (GEFs) play essential roles in regulating the activity of small GTPases. Several GAPs and GEFs have been shown to be present at the postsynaptic density (PSD) within excitatory glutamatergic neurons and regulate the activity of glutamate receptors. However, it is not known how synaptic GAP and GEF proteins are organized within the PSD signaling machinery, if they have overlapping interaction networks, or if they associate with proteins implicated in contributing to psychiatric disease...
July 13, 2017: Scientific Reports
K-J Fan, Y Liu, B Yang, X-D Tian, C-R Li, B Wang
OBJECTIVE: The purpose of this study was to explore whether long non-coding RNA AGAP2-AS1 (AGAP2-AS1) could serve as a novel biomarker for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Cancer and matched normal lung tissues were collected from 198 patients. AGAP2-AS1 levels were examined by RT-PCR, and the associations of AGAP2-AS1 levels with clinicopathological characteristics evaluated. Overall survival was evaluated using the Kaplan-Meier method...
May 2017: European Review for Medical and Pharmacological Sciences
Teresa Vitali, Sofia Girald-Berlingeri, Paul A Randazzo, Pei-Wen Chen
ADP-ribosylation factors (Arfs) are members of the Ras GTPase superfamily. The function of Arfs is dependent on GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. Arf GAPs have been shown to be present in integrin adhesion complexes, which include focal adhesions. Integrin adhesion complexes are composed of integrins, scaffolding proteins and signaling proteins and regulate cell proliferation, survival, differentiation and migration...
March 31, 2017: Small GTPases
Fuzhen Qi, Xianghua Liu, Hao Wu, Xiang Yu, Chenchen Wei, Xiaodan Huang, Guozhong Ji, Fengqi Nie, Keming Wang
BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as important regulators of tumorigenesis and cancer progression. Recently, the lncRNA AGAP2-AS1 was identified as an oncogenic lncRNA in human non-small cell lung cancer (NSCLC) and its elevated expression was linked to NSCLC development and progression. However, the expression pattern and molecular mechanism of AGAP2-AS1 in gastric cancer (GC) have not been characterized. METHODS: Bioinformatic analysis was performed to determine AGAP2-AS1 expression levels in the GC and normal tissues using gene profiling data from the Gene Expression Omnibus...
February 16, 2017: Journal of Hematology & Oncology
Sung-Eun Kim, Jinsil Choo, Joon Yoon, Jae Ryang Chu, Yun Jung Bae, Seungyeoun Lee, Taesung Park, Mi-Kyung Sung
Obesity-induced chronic inflammation is known to increase the risk of ulcerative colitis, Crohn's disease, and colorectal cancer. Accumulating evidence suggests that leptin and insulin are key molecules linking obesity with diseases of the lower intestine. Here, we identified serum phenotype-associated genes in the colon of diet-induced obese mice as early biomarkers of obesity-associated colonic diseases. C57BL/6J mice were fed with either normal diet (ND, 15% of fat calories) or high-fat diet (HFD, 45% of fat calories) for 8 weeks...
2017: PloS One
Wen Wang, Fan Yang, Lu Zhang, Jing Chen, Zheng Zhao, Haoyuan Wang, Fan Wu, Tingyu Liang, Xiaoyan Yan, Jiye Li, Qing Lan, Jiangfei Wang, Jizong Zhao
Anaplastic glioma is Grade III and the median overall survival is about 37.6 months. However, there are still other factors that affect the prognosis for anaplastic glioma patients due to variable overall survival. So we screened four-lncRNA signature (AGAP2-AS1, TPT1-AS1, LINC01198 and MIR155HG) from the lncRNA expression profile from the GSE16011, CGGA and REMBRANDT datasets. The patients in low risk group had longer overall survival than high risk group (median OS 2208.25 vs. 591.30 days; P < 0.0001)...
November 22, 2016: Oncotarget
W Li, M Sun, C Zang, P Ma, J He, M Zhang, Z Huang, Y Ding, Y Shu
Recently, long non-coding RNAs (lncRNAs) are identified as new crucial regulators of diverse cellular processes, including cell proliferation, differentiation and cancer cells metastasis. Accumulating evidence has revealed that aberrant lncRNA expression plays important roles in carcinogenesis and tumor progression. However, the expression pattern and biological function of lncRNAs in non-small-cell lung cancer (NSCLC) remain largely unknown. In this study, we performed comprehensive analysis of lncRNA expression in human NSCLC samples by using microarray data from Gene Expression Omnibus...
May 19, 2016: Cell Death & Disease
Meng-Yao Li, Feng Wang, Qian Jiang, Guan-Long Wang, Chang Tian, Ai-Sheng Xiong
A suitable reference gene is an important prerequisite for guarantying accurate and reliable results in qPCR analysis. Celery is one of the representative vegetable in Apiaceae and is widely cultivated and consumed in the world. However, no reports have been previously published concerning reference genes in celery. In this study, the expression stabilities of nine candidate reference genes in leaf blade and petiole at different development stages were evaluated using three statistics algorithms geNorm, NormFinder, and BestKeeper...
2016: Frontiers in Plant Science
Doo-Sik Kong, Jinkuk Kim, In-Hee Lee, Sung Tae Kim, Ho Jun Seol, Jung-Il Lee, Woong-Yang Park, Gyuha Ryu, Zichen Wang, Avi Ma'ayan, Do-Hyun Nam
We postulated that multicentric glioblastoma (GBM) represents more invasiveness form than solitary GBM and has their own genomic characteristics. From May 2004 to June 2010 we retrospectively identified 51 treatment-naïve GBM patients with available clinical information from the Samsung Medical Center data registry. Multicentricity of the tumor was defined as the presence of multiple foci on the T1 contrast enhancement of MR images or having high signal for multiple lesions without contiguity of each other on the FLAIR image...
March 8, 2016: Oncotarget
Min Yuan, Jingxin Cheng, Yaxin Liu, Wei Su, Yu Zhang, Yi Zhang
OBJECTIVE: To explore the differential expression of microRNA (miRNA) in HPV16-positive squamous carcinoma of the cervix in the Uygur of southern Xinjiang and to predict the target genes of the miRNAs.
 METHODS: Samples of HPV16-positive squamous carcinoma of the cervix from 5 Uygurs were collected for miRNA microarray assay. The differentially expressed miRNAs were selected for further verification by real-time quantitative RT-PCR. The software, including targetscan, miRwalk, miRanda and pictar, were used to predict the target genes of the verified miRNAs...
July 2015: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Tao Huang, Jing Yang, Yu-Dong Cai
The mechanisms of lung cancer are highly complex. Not only mRNA gene expression but also microRNAs, DNA methylation, and copy number variation (CNV) play roles in tumorigenesis. It is difficult to incorporate so much information into a single model that can comprehensively reflect all these lung cancer mechanisms. In this study, we analyzed the 129 TCGA (The Cancer Genome Atlas) squamous cell lung carcinoma samples with gene expression, microRNA expression, DNA methylation, and CNV data. First, we used variance inflation factor (VIF) regression to build the whole genome integrative network...
2015: BioMed Research International
Susan Dwane, Edel Durack, Rosemary O'Connor, Patrick A Kiely
RACK1 binds proteins in a constitutive or transient manner and supports signal transmission by engaging in diverse and distinct signalling pathways. The emerging theme is that RACK1 functions as a signalling switch, recruiting proteins to form distinct molecular complexes. In focal adhesions, RACK1 is required for the regulation of FAK activity and for integrating a wide array of cellular signalling events including the integration of growth factor and adhesion signalling pathways. FAK is required for cell adhesion and migration and has a well-established role in neurite outgrowth and in the developing nervous system...
January 2014: Cellular Signalling
Yuanjun Wu, Yu Zhao, Xiaojie Ma, Yunjuan Zhu, Jaimin Patel, Zhongzhen Nie
AGAP2 [Arf (ADP-ribosylation factor) GAP (GTPase-activating protein) with GTP-binding-protein-like, ankyrin repeat and PH (pleckstrin homology) domains] is a multidomain Arf GAP that was shown to promote the fast recycling of transferrin receptors. In the present study we tested the hypothesis that AGAP2 regulates the trafficking of β2-adrenergic receptors. We found that AGAP2 formed a complex with β-arrestin1 and β-arrestin2, proteins that are known to regulate β2-adrenergic receptor signalling and trafficking...
June 15, 2013: Biochemical Journal
Ruibai Luo, Itoro O Akpan, Ryo Hayashi, Marek Sramko, Valarie Barr, Yoko Shiba, Paul A Randazzo
AGAPs are a subtype of Arf GTPase-activating proteins (GAPs) with 11 members in humans. In addition to the Arf GAP domain, the proteins contain a G-protein-like domain (GLD) with homology to Ras superfamily proteins and a PH domain. AGAPs bind to clathrin adaptors, function in post Golgi membrane traffic, and have been implicated in glioblastoma. The regulation of AGAPs is largely unexplored. Other enzymes containing GTP binding domains are regulated by nucleotide binding. However, nucleotide binding to AGAPs has not been detected...
May 18, 2012: Journal of Biological Chemistry
Yoko Shiba, Winfried Römer, Gonzalo A Mardones, Patricia V Burgos, Christophe Lamaze, Ludger Johannes
The retrograde transport route links early endosomes and the TGN. Several endogenous and exogenous cargo proteins use this pathway, one of which is the well-explored bacterial Shiga toxin. ADP-ribosylation factors (Arfs) are approximately 20 kDa GTP-binding proteins that are required for protein traffic at the level of the Golgi complex and early endosomes. In this study, we expressed mutants and protein fragments that bind to Arf-GTP to show that Arf1, but not Arf6 is required for transport of Shiga toxin from early endosomes to the TGN...
July 15, 2010: Journal of Cell Science
Ethan Cerami, Emek Demir, Nikolaus Schultz, Barry S Taylor, Chris Sander
BACKGROUND: Glioblastoma multiforme (GBM) is the most common and aggressive type of brain tumor in humans and the first cancer with comprehensive genomic profiles mapped by The Cancer Genome Atlas (TCGA) project. A central challenge in large-scale genome projects, such as the TCGA GBM project, is the ability to distinguish cancer-causing "driver" mutations from passively selected "passenger" mutations. PRINCIPAL FINDINGS: In contrast to a purely frequency based approach to identifying driver mutations in cancer, we propose an automated network-based approach for identifying candidate oncogenic processes and driver genes...
February 12, 2010: PloS One
Yunjuan Zhu, Yuanjun Wu, Jae I Kim, Zhimin Wang, Yehia Daaka, Zhongzhen Nie
Focal adhesions are specialized sites of cell attachment to the extracellular matrix where integrin receptors link extracellular matrix to the actin cytoskeleton, and they are constantly remodeled during cell migration. Focal adhesion kinase (FAK) is an important regulator of focal adhesion remodeling. AGAP2 is an Arf GTPase-activating protein that regulates endosomal trafficking and is overexpressed in different human cancers. Here we examined the regulation of the FAK activity and the focal adhesion remodeling by AGAP2...
May 15, 2009: Journal of Biological Chemistry
Jillian L Dunphy, Keqiang Ye, James E Casanova
BRAG2 is a guanine nucleotide exchange factor for the GTPase Arf6 that cycles between the cytoplasm and nucleus in a CRM1/exportin1-dependent manner. Despite its presence in the nucleus, nuclear functions have not previously been described. Here, we show that depletion of endogenous BRAG2 by RNAi leads to an increased number of Cajal bodies (CBs), and altered structure of nucleoli, as indicated by less focal fibrillarin staining. This result was surprising given that nuclear BRAG2 is diffusely distributed throughout the nucleoplasm and is not concentrated within nucleoli at steady state...
June 2007: Traffic
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