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https://www.readbyqxmd.com/read/29287593/upregulation-of-citrullination-pathway-from-autoimmune-to-idiopathic-lung-fibrosis
#1
Katerina D Samara, Athina Trachalaki, Eliza Tsitoura, Anastasios V Koutsopoulos, Eleni D Lagoudaki, Ismini Lasithiotaki, George Margaritopoulos, Panagiotis Pantelidis, Eleni Bibaki, Nikolaos M Siafakas, Nikolaos Tzanakis, Athol U Wells, Katerina M Antoniou
BACKGROUND: Increased protein citrullination and peptidylarginine deiminases (PADIs), which catalyze the citrullination process, are central in Rheumatoid arthritis pathogenesis and probably involved in the initial steps towards autoimmunity. Approximately, 10% of RA patients develop clinically significantly ILD. A possible shared role of protein citrullination in rheumatoid arthritis associated interstitial lung disease (RA-ILD), and idiopathic pulmonary fibrosis (IPF) pathogenesis remains unclear...
December 29, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29148420/the-expression-of-mrna-for-peptidylarginine-deiminase-type-2-and-type-4-in-bone-marrow-cd34-cells-in-rheumatoid-arthritis
#2
Tatsuo Nagai, Yu Matsueda, Tetsuya Tomita, Hideki Yoshikawa, Shunsei Hirohata
OBJECTIVES: Antibodies directed to citrullinated proteins are highly specific for rheumatoid arthritis (RA). Citrullination is catalyzed by peptidylarginine deiminase (PAD) enzymes. The current study examined the mRNA expression of PADI2 and PADI4 in bone marrow (BM) CD34+ cells from RA patients. METHODS: CD34+ cells were purified from BM samples obtained from 48 RA patients and from 30 osteoarthritis (OA) patients during joint operations via aspiration from the iliac crest...
November 14, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29084334/association-between-brain-gene-expression-dna-methylation-and-alteration-of-ex-vivo-magnetic-resonance-imaging-transverse-relaxation-in-late-life-cognitive-decline
#3
Lei Yu, Robert J Dawe, Patricia A Boyle, Chris Gaiteri, Jingyun Yang, Aron S Buchman, Julie A Schneider, Konstantinos Arfanakis, Philip L De Jager, David A Bennett
Importance: Alteration of ex vivo magnetic resonance imaging transverse relaxation is associated with late-life cognitive decline even after controlling for common neuropathologic conditions. However, the underlying neurobiology of this association is unknown. Objective: To investigate the association between brain gene expression, DNA methylation, and alteration of magnetic resonance imaging transverse relaxation in late-life cognitive decline. Design, Setting, and Participants: Data came from 2 community-based longitudinal cohort studies of aging and dementia, the Religious Orders Study, which began in 1993, and the Rush Memory and Aging Project, which began in 1997...
December 1, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/29050308/the-lncrna-hoxa11-as-functions-as-a-competing-endogenous-rna-to-regulate-padi2-expression-by-sponging-mir-125a-5p-in-liver-metastasis-of-colorectal-cancer
#4
Dong Chen, Qiang Sun, Lufei Zhang, Xiaohu Zhou, Xiaofei Cheng, Dongkai Zhou, Feng Ye, Jianjiang Lin, Weilin Wang
Several long non-coding RNAs (lncRNAs) play important roles in the regulation of liver metastasis in colorectal cancer (CRC) patients. We previously described the potential involvement of HOMEOBOX A11 (HOXA11) antisense RNA (HOXA11-AS), miR-125a-5p, and peptidyl arginine deiminase 2 (PADI2) in promoting liver metastasis in CRC patients. In the present study, we verified the significant upregulation of HOXA11-AS and PADI2, as well as the downregulation of miR-125a-5p, in CRC patients with liver metastasis. Overexpression and knockdown studies of HOXA11-AS or PADI2, as well as gain-/loss-of-function studies of miR-125a-5p, revealed a positive correlation between HOXA11-AS and PADI2 and a negative correlation with miR-125a-5p in the regulation of liver metastasis in CRC cell lines...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28819028/padi2-mediated-citrullination-promotes-prostate-cancer-progression
#5
Lin Wang, Guanhua Song, Xiang Zhang, Tingting Feng, Jihong Pan, Weiwen Chen, Muyi Yang, Xinnuo Bai, Yu Pang, Jindan Yu, Jinxiang Han, Bo Han
Onset of castration-resistance prostate cancer (CRPC) after long-term androgen deprivation therapy remains a major obstacle in the treatment of prostate cancer. The peptidylarginine deiminase PADI2 has been implicated in chronic inflammatory diseases and cancer. Here we show that PADI2 is an androgen-repressed gene and is upregulated in CRPC. PADI2 expression was required for survival and cell-cycle progression of prostate cancer cells, and PADI2 promoted proliferation of prostate cancer cells under androgen-deprived or castration conditions in vitro and in vivo Cytoplasmic PADI2 protected the androgen receptor (AR) against proteasome-mediated degradation and facilitated AR binding to its target genes after nuclear translocation and citrullination of histone H3 amino acid residue R26...
November 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28617813/identification-of-padi2-as-a-novel-angiogenesis-regulating-gene-by-genome-association-studies-in-mice
#6
Mehrdad Khajavi, Yi Zhou, Amy E Birsner, Lauren Bazinet, Amanda Rosa Di Sant, Alex J Schiffer, Michael S Rogers, Subrahmanian Tarakkad Krishnaji, Bella Hu, Vy Nguyen, Leonard Zon, Robert J D'Amato
Recent findings indicate that growth factor-driven angiogenesis is markedly influenced by genetic variation. This variation in angiogenic responsiveness may alter the susceptibility to a number of angiogenesis-dependent diseases. Here, we utilized the genetic diversity available in common inbred mouse strains to identify the loci and candidate genes responsible for differences in angiogenic response. The corneal micropocket neovascularization assay was performed on 42 different inbred mouse strains using basic fibroblast growth factor (bFGF) pellets...
June 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28549415/role-of-peptidylarginine-deiminase-2-pad2-in-mammary-carcinoma-cell-migration
#7
Sachi Horibata, Katherine E Rogers, David Sadegh, Lynne J Anguish, John L McElwee, Pragya Shah, Paul R Thompson, Scott A Coonrod
BACKGROUND: Penetration of the mammary gland basement membrane by cancer cells is a crucial first step in tumor invasion. Using a mouse model of ductal carcinoma in situ, we previously found that inhibition of peptidylarginine deiminase 2 (PAD2, aka PADI2) activity appears to maintain basement membrane integrity in xenograft tumors. The goal of this investigation was to gain insight into the mechanisms by which PAD2 mediates this process. METHODS: For our study, we modulated PAD2 activity in mammary ductal carcinoma cells by lentiviral shRNA-mediated depletion, lentiviral-mediated PAD2 overexpression, or PAD inhibition and explored the effects of these treatments on changes in cell migration and cell morphology...
May 26, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28403548/protein-arginine-deiminase-2-suppresses-proliferation-of-colon-cancer-cells-through-protein-citrullination
#8
Ryo Funayama, Hajime Taniguchi, Masamichi Mizuma, Fumiyoshi Fujishima, Minoru Kobayashi, Shinobu Ohnuma, Michiaki Unno, Keiko Nakayama
Expression of the gene for protein-arginine deiminase 2 (PADI2) has been shown to be downregulated in colon cancer, with such downregulation being indicative of a poor prognosis in individuals with this disease. We have now examined the expression of PADI2 in matched colon cancer and normal colon tissue specimens as well as in colon cancer cell lines. We found that isoform 1 of PADI2 is the predominant isoform in colon tissue and is downregulated during colon carcinogenesis. Immunohistochemical analysis showed that PADI2 is expressed in normal colonic epithelial cells...
April 2017: Cancer Science
https://www.readbyqxmd.com/read/28331341/investigating-the-expression-effect-and-tumorigenic-pathway-of-padi2-in-tumors
#9
Wei Guo, Yabing Zheng, Bing Xu, Fang Ma, Chang Li, Xiaoqian Zhang, Yao Wang, Xiaotian Chang
BACKGROUND: Peptidylarginine deiminase (PAD) catalyzes the conversion of arginine residues to citrulline residues, termed citrullination. Recent studies have suggested that PAD isoform 2 (PADI2) plays an important role in tumors, although its tumorigenic effect and mechanism are largely unknown. MATERIALS AND METHODS: Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were used to investigate the expression level of PADI2 in various tumor tissues and patient blood samples, respectively...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28229027/risk-analysis-of-colorectal-cancer-incidence-by-gene-expression-analysis
#10
Wei-Chuan Shangkuan, Hung-Che Lin, Yu-Tien Chang, Chen-En Jian, Hueng-Chuen Fan, Kang-Hua Chen, Ya-Fang Liu, Huan-Ming Hsu, Hsiu-Ling Chou, Chung-Tay Yao, Chi-Ming Chu, Sui-Lung Su, Chi-Wen Chang
BACKGROUND: Colorectal cancer (CRC) is one of the leading cancers worldwide. Several studies have performed microarray data analyses for cancer classification and prognostic analyses. Microarray assays also enable the identification of gene signatures for molecular characterization and treatment prediction. OBJECTIVE: Microarray gene expression data from the online Gene Expression Omnibus (GEO) database were used to to distinguish colorectal cancer from normal colon tissue samples...
2017: PeerJ
https://www.readbyqxmd.com/read/27485256/simple-and-rapid-characterization-of-novel-large-germline-deletions-in-sdhb-sdhc-and-sdhd-related-paraganglioma
#11
A S Hoekstra, B van den Ende, X P Julià, L van Breemen, K Scheurwater, C M Tops, A Malinoc, P Devilee, H P H Neumann, J-P Bayley
Germline mutations in genes encoding subunits of succinate dehydrogenase (SDH) are associated with hereditary paraganglioma and pheochromocytoma. Although most mutations in SDHB, SDHC and SDHD are intraexonic variants, large germline deletions may represent up to 10% of all variants but are rarely characterized at the DNA sequence level. Additional phenotypic effects resulting from deletions that affect neighboring genes are also not understood. We performed multiplex ligation-dependent probe amplification, followed by a simple long-range PCR 'chromosome walking' protocol to characterize breakpoints in 20 SDHx-linked paraganglioma-pheochromocytoma patients...
April 2017: Clinical Genetics
https://www.readbyqxmd.com/read/27478411/padi2-gene-confers-susceptibility-to-breast-cancer-and-plays-tumorigenic-role-via-acsl4-binc3-and-ca9-signaling
#12
Huifeng Wang, Bing Xu, Xiaoqian Zhang, Yabing Zheng, Yan Zhao, Xiaotian Chang
BACKGROUND: Peptidylarginine deiminase (PAD) post-translationally converts arginine residues to citrulline residues. Recent studies have suggested that PADI2 (PAD isoform 2), a member of the PAD family, is involved in the tumorigenic process of some tumors, especially breast cancer. However, little is known about the mechanisms of PADI2 in tumorigenesis. This study aimed to elucidate the tumorigenic role and regulatory pathway of PADI2 in breast tumors. METHODS: The Sequenom MassARRAY and TaqMan genotyping methods were used to investigate the correlation between PADI2 gene SNPs and various tumor risks...
2016: Cancer Cell International
https://www.readbyqxmd.com/read/27425813/targeting-padi2-could-stop-the-progression-of-myeloma
#13
Sanjay Tanday
No abstract text is available yet for this article.
August 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27400413/citrullination-of-histone-h3-drives-il-6-production-by-bone-marrow-mesenchymal-stem-cells-in-mgus-and-multiple-myeloma
#14
G McNee, K L Eales, W Wei, D S Williams, A Barkhuizen, D B Bartlett, S Essex, S Anandram, A Filer, P A H Moss, G Pratt, S Basu, C C Davies, D A Tennant
Multiple myeloma (MM), an incurable plasma cell malignancy, requires localisation within the bone marrow. This microenvironment facilitates crucial interactions between the cancer cells and stromal cell types that permit the tumour to survive and proliferate. There is increasing evidence that the bone marrow mesenchymal stem cell (BMMSC) is stably altered in patients with MM-a phenotype also postulated to exist in patients with monoclonal gammopathy of undetermined significance (MGUS) a benign condition that precedes MM...
February 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27280713/downregulation-of-the-deiminase-padi2-is-an-early-event-in-colorectal-carcinogenesis-and-indicates-poor-prognosis
#15
Neus Cantariño, Eva Musulén, Vanesa Valero, Miquel Angel Peinado, Manuel Perucho, Victor Moreno, Sònia-Vanina Forcales, Julien Douet, Marcus Buschbeck
UNLABELLED: Peptidyl arginine deiminases (PADI) are a family of enzymes that catalyze the poorly understood posttranslational modification converting arginine residues into citrullines. In this study, the role of PADIs in the pathogenesis of colorectal cancer was investigated. Specifically, RNA expression was analyzed and its association with survival in a cohort of 98 colorectal cancer patient specimens with matched adjacent mucosa and 50 controls from donors without cancer. Key results were validated in an independent collection of tumors with matched adjacent mucosa and by mining of a publicly available expression data set...
September 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27150598/decreased-severity-of-experimental-autoimmune-arthritis-in-peptidylarginine-deiminase-type-4-knockout-mice
#16
Akari Suzuki, Yuta Kochi, Hirofumi Shoda, Yu Seri, Keishi Fujio, Tetsuji Sawada, Ryo Yamada, Kazuhiko Yamamoto
BACKGROUND: Peptidylarginine deiminase type 4 (PADI4) has been identified as a susceptibility gene for rheumatoid arthritis (RA) by genome-wide association studies. PADI4 is highly expressed in the bone marrow, macrophages, neutrophils, and monocytes. Peptidyl citrulline is an interesting molecule in RA because it is a target antigen for anti-citrullinated peptide antibodies, and only PADs (translated proteins from PADI genes) can provide peptidyl citrulline via the modification of protein substrates...
May 5, 2016: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/27074337/a-cellular-model-reflecting-the-phenotypic-heterogeneity-of-mutant-hras-driven-squamous-cell-carcinoma
#17
Neus Cantariño, M Teresa Fernández-Figueras, Vanesa Valero, Eva Musulén, Roberto Malinverni, Isabel Granada, Stephen J Goldie, Juan Martín-Caballero, Julien Douet, Sonia-Vanina Forcales, Marcus Buschbeck
Squamous cell carcinomas have a range of histopathological manifestations. The parameters that determine this clinically observed heterogeneity are not fully understood. Here, we report the generation of a cell culture model that reflects part of this heterogeneity. We have used the catalytic subunit of human telomerase hTERT and large T to immortalize primary UV-unexposed keratinocytes. Then, mutant HRAS G12V has been introduced to transform these immortal keratinocytes. When injected into immunosuppressed mice, transformed cells grew as xenografts with distinct histopathological characteristics...
September 1, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27060082/identification-of-citrullinated-peptides-in-the-synovial-fluid-of-patients-with-rheumatoid-arthritis-using-lc-maldi-tof-tof
#18
Fei Wang, Fang-Fang Chen, Wen-Bo Gao, Hai-Yong Wang, Ning-Wei Zhao, Min Xu, De-Yu Gao, Wei Yu, Xiao-Ling Yan, Jian-Ning Zhao, Xiao-Jun Li
The objective of the study is to investigate potential citrullinated autoantigens as targets of anti-citrullinated protein antibodies (ACPAs) response in synovial fluids (SFs) of patients with rheumatoid arthritis (RA). SFs from six RA patients and six osteoarthritis (OA) patients as controls were collected. The citrullinated proteins in SFs were extracted by immunoprecipitation with rabbit anti-citrulline antibodies. Matrix-assisted laser desorption/ionization time of flight mass spectrometry/time of flight mass spectrometry (MALDI-TOF/TOF) mass spectrometry was subsequently performed to discover a characteristic neutral loss to finally determine citrullinated autoantigens...
September 2016: Clinical Rheumatology
https://www.readbyqxmd.com/read/26927695/significant-impact-of-mirna-target-gene-networks-on-genetics-of-human-complex-traits
#19
Yukinori Okada, Tomoki Muramatsu, Naomasa Suita, Masahiro Kanai, Eiryo Kawakami, Valentina Iotchkova, Nicole Soranzo, Johji Inazawa, Toshihiro Tanaka
The impact of microRNA (miRNA) on the genetics of human complex traits, especially in the context of miRNA-target gene networks, has not been fully assessed. Here, we developed a novel analytical method, MIGWAS, to comprehensively evaluate enrichment of genome-wide association study (GWAS) signals in miRNA-target gene networks. We applied the method to the GWAS results of the 18 human complex traits from >1.75 million subjects, and identified significant enrichment in rheumatoid arthritis (RA), kidney function, and adult height (P < 0...
March 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/26627478/messenger-rna-profile-analysis-deciphers-new-esrrb-responsive-genes-in-prostate-cancer-cells
#20
Yuan Lu, Jilong Li, Jianlin Cheng, Dennis B Lubahn
BACKGROUND: Orphan nuclear receptor estrogen related receptor β (Esrrb or ERRβ) is well known in stem cells and early embryonic development. However, little is known about its function in cancer. METHOD: We investigated the mRNA profile alterations induced by Esrrb expression and its synthetic ligand DY131 in human prostate cancer DU145 cells via RNA-Seq analysis. RESULTS: We distinguished 67 mRNAs differentially expressed by Esrrb alone...
December 1, 2015: BMC Molecular Biology
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