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Ingvild S M Gabrielsen, Silja Svanstrøm Amundsen, Hanna Helgeland, Siri Tennebø Flåm, Nimo Hatinoor, Kristian Holm, Marte K Viken, Benedicte A Lie
Genome-wide association studies (GWAS) have boosted our knowledge of genetic risk variants in autoimmune diseases (AIDs). Most risk variants are located within or near genes with immunological functions, and the majority is found to be non-coding, pointing towards a regulatory role. In this study, we performed a cis expression quantitative trait locus (eQTL) screen restricted to 353 AID associated risk variants selected from the GWAS catalog to investigate whether these single nucleotide polymorphisms (SNPs) influence gene expression in thymus...
May 19, 2016: Human Molecular Genetics
Davide Tonduti, Simona Orcesi, Emma M Jenkinson, Imen Dorboz, Florence Renaldo, Celeste Panteghini, Gillian I Rice, Marco Henneke, John H Livingston, Monique Elmaleh, Lydie Burglen, Michèl A A P Willemsen, Luisa Chiapparini, Barbara Garavaglia, Diana Rodriguez, Odile Boespflug-Tanguy, Isabella Moroni, Yanick J Crow
BACKGROUND: Cystic leukoencephalopathy without megalencephaly is a disorder related in some cases to RNASET2 mutations and characterized by bilateral anterior temporal subcortical cysts and multifocal lobar white matter lesions with sparing of central white matter structures. This phenotype significantly overlaps with the sequelae of in utero cytomegalovirus (CMV) infection, including the presence of intracranial calcification in some cases. Aicardi-Goutières syndrome (AGS) is another inherited leukodystrophy with cerebral calcification mimicking congenital infection...
July 2016: European Journal of Paediatric Neurology: EJPN
Levava Roiz, Patricia Smirnoff, Iris Lewin, Oded Shoseyov, Betty Schwartz
The roles of cell motility and angiogenetic processes in metastatic spread and tumor aggressiveness are well established and must be simultaneously targeted to maximize antitumor drug potency. This work evaluated the antitumorigenic capacities of human recombinant RNASET2 (hrRNASET2), a homologue of the Aspergillus niger T2RNase ACTIBIND, which has been shown to display both antitumorigenic and antiangiogenic activities. hrRNASET2 disrupted intracellular actin filament and actin-rich extracellular extrusion organization in both CT29 colon cancer and A375SM melanoma cells and induced a significant dose-dependent inhibition of A375SM cell migration...
2016: Oncoscience
Qianqian Wang, Xiuxiu Wang, Yan Le, Min Jiang, Jiaqiang Wu, Li Tao, Yuli Kang, Leihong Xiang
BACKGROUND: Impaired dendrite outgrowth of melanocytes is one of the reasons triggering vitiligo. RNASET2 was identified as one of the risk genes for vitiligo in a GWAS study conducted in the Chinese Han population. However, the role of Rnaset2 in the outgrowth of melanocytes is rarely studied. OBJECTIVE: This study is to investigate the effects of Rnaset2 in regulating the outgrowth of melanocytes and its interacting proteins. METHODS: Stress conditions (UV irradiation, hydrogen peroxide, and lipopolysaccharides) were applied to primary human epidermal melanocytes (HEMs) and epidermal keratinocytes (HEKs)...
October 2015: Journal of Dermatological Science
G Caputa, S Zhao, A E G Criado, D S Ory, J G Duncan, J E Schaffer
RNASET2 is a ubiquitously expressed acidic ribonuclease that has been implicated in diverse pathophysiological processes including tumorigeneis, vitiligo, asthenozoospermia, and neurodegeneration. Prior studies indicate that RNASET2 is induced in response to oxidative stress and that overexpression of RNASET2 sensitizes cells to reactive oxygen species (ROS)-induced cell death through a mechanism that is independent of catalytic activity. Herein, we report a loss-of-function genetic screen that identified RNASET2 as an essential gene for lipotoxic cell death...
February 2016: Cell Death and Differentiation
Qianqian Wang, Xiuxiu Wang, Leihong Xiang
No abstract text is available yet for this article.
July 2015: Journal of Investigative Dermatology. Symposium Proceedings
Xiao-jun Chen, Xiao-hua Gong, Ni Yan, Shuai Meng, Qiu Qin, Yan-Fei Jiang, Hai-Yan Zheng, Jin-an Zhang
BACKGROUND: Polymorphisms of the CC chemokine receptor 6 (CCR6) and RNASET2 tag SNP have been shown to be associated with the susceptibility to several immune-related diseases. This study was conducted to identify the association of CCR6 and RNASET2 tag SNP with autoimmune thyroid diseases (AITDs) in the Chinese Han population. METHODS: We enrolled 1061 patients with AITDs, including 701 patients with Graves' disease (GD) and 360 patients with Hashimoto's thyroiditis (HT), and 938 healthy individuals for a case-control genetic association study...
2015: BMC Medical Genetics
Liron Nesiel-Nuttman, Shani Doron, Betty Schwartz, Oded Shoseyov
Human RNASET2 (hRNASET2) has been demonstrated to exert antiangiogenic and antitumorigenic effects independent of its ribonuclease capacity. We suggested that RNASET2 exerts its antiangiogenic and antitumorigenic activities via binding to actin and consequently inhibits cell motility. We focused herein on the identification of the actin binding site of hRNASET2 using defined sequences encountered within the whole hRNASET2 protein. For that purpose we designed 29 different hRNASET2-derived peptides. The 29 peptides were examined for their ability to bind immobilized actin...
2015: Oncoscience
Marta Lualdi, Edoardo Pedrini, Katia Rea, Laura Monti, Debora Scaldaferri, Marzia Gariboldi, Annalisa Camporeale, Paolo Ghia, Elena Monti, Antonella Tomassetti, Francesco Acquati, Roberto Taramelli
As widely recognized, tumor growth entails a close and complex cross-talk among cancer cells and the surrounding tumor microenvironment. We recently described the human RNASET2 gene as one key player of such microenvironmental cross-talk. Indeed, the protein encoded by this gene is an extracellular RNase which is able to control cancer growth in a non-cell autonomous mode by inducing a sustained recruitment of immune-competent cells belonging to the monocyte/macrophage lineage within a growing tumor mass. Here, we asked whether this oncosuppressor gene is sensitive to stress challenges and whether it can trigger cell-intrinsic processes as well...
April 10, 2015: Oncotarget
Marta Lualdi, Edoardo Pedrini, Francesca Petroni, Johnny Näsman, Christer Lindqvist, Debora Scaldaferri, Roberto Taramelli, Antonio Inforzato, Francesco Acquati
Ribonucleases form a large family of enzymes involved in RNA metabolism and are endowed with a broad range of biological functions. Among the different RNase proteins described in the last decades, those belonging to the Rh/T2/S subfamily show the highest degree of evolutionary conservation, suggesting the occurrence of a key critical ancestral role for this protein family. We have recently defined the human RNASET2 gene as a novel member of a group of oncosuppressors called "tumor antagonizing genes," whose activity in the control of cancer growth is carried out mainly in vivo...
June 2015: Molecular Biotechnology
Liron Nesiel-Nuttman, Betty Schwartz, Oded Shoseyov
Human RNASET2 has been implicated in antitumorigenic and antiangiogenic activities, independent of its ribonuclease capacities. We constructed a truncated version of human RNASET2, starting at E50 (trT2-50) and devoid of ribonuclease activity. trT2-50 maintained its ability to bind actin and to inhibit angiogenesis and tumorigenesis. trT2-50 binds to cell surface actin and formed a complex with actin in vitro. The antiangiogenic effect of this protein was demonstrated in human umbilical vein endothelial cells (HUVECs) by its ability to arrest tube formation on Matrigel, induced by angiogenic factors...
November 30, 2014: Oncotarget
Fuqiang Yin, Ling Liu, Xia Liu, Gang Li, Li Zheng, Danrong Li, Qi Wang, Wei Zhang, Li Li
Ribonuclease T2 (RNASET2) and gametogenetin binding protein 2 (GGNBP2) are tumor suppressor genes whose expression is downregulated in ovarian and other types of cancer. However, whether the proteins encoded by these genes are associated with drug resistance has rarely been studied. Using real-time quantitative polymerase chain reaction, in the present study we showed that RNASET2 and GGNBP2 mRNA levels were significantly lower in A2780-CBP (carboplatin-resistant) and A2780-DDP (cisplatin-resistant) ovarian cancer cells than in the parental A2780 cells and were downregulated in drug-resistant ovarian cancer tissues compared with their drug-sensitive counterparts...
July 2014: Oncology Reports
Q Wang, M Jiang, J Wu, Y Ma, T Li, Q Chen, X Zhang, L Xiang
The recent genome-wide association study identified a link between vitiligo and genetic variants in the ribonuclease T2 (RNASET2) gene; however, the functional roles of RNASET2 in vitiligo pathogenesis or in melanocyte apoptosis have yet to be determined. The current study was designed to investigate the vitiligo-related expression pattern of RNASET2 and its molecular function involving apoptosis-related signaling proteins and pathways. The results showed overexpression of RNASET2 in epidermis specimens from 40 vitiligo patients compared with that from matched healthy controls...
2014: Cell Death & Disease
John H Livingston, Stavros Stivaros, Dan Warren, Yanick J Crow
Intracranial calcification (ICC) is a common finding on neuroimaging in paediatric neurology practice. In approximately half of all cases the calcification occurs in damaged, neoplastic, or malformed brain. For the large number of other disorders in which ICC occurs, no common pathogenetic mechanism can be suggested. Congenital infection, particularly with cytomegalovirus, accounts for a significant proportion of all cases. However, some genetic diseases, in particular Aicardi-Goutières syndrome, Band-like calcification, and RNASET2-related disease, may mimic congenital infection; therefore, a full consideration of the radiological and clinical features is necessary before concluding that congenital infection is the cause...
July 2014: Developmental Medicine and Child Neurology
Yanquan Xu, Wenjun Chen, Meng Bian, Xiaoyun Wang, Jiufeng Sun, Hengchang Sun, Feifei Jia, Chi Liang, Xuerong Li, Xiaonong Zhou, Yan Huang, Xinbing Yu
BACKGROUND: Clonorchis sinensis (C. sinensis, Cs) is a trematode parasite that often causes chronic cumulative infections in the hepatobiliary ducts of the host and can lead to pathological changes by continuously released excretory/secretory proteins (ESPs). A T2 ribonuclease in trematode ESPs, has been identified as a potent regulator of dendritic cell (DCs) modulation. We wondered whether there was a counterpart present in CsESPs with similar activity. To gain a better understanding of CsESPs associated immune responses, we identified and characterized RNASET2 of C...
2013: Parasites & Vectors
Bao-ping Wang, Lin Han, Jing-jie Tong, Yan Wang, Zhao-tong Jia, Ming-xia Sun, Hai-li Wang
OBJECTIVE: To assess the association of RNASET2 gene polymorphisms and haplotypes with Graves disease (GD) in Han Chinese population from coastal regions of Shandong Province. METHODS: A total of 471 GD patients and 472 controls were enrolled. Genotypes of single nucleotide polymorphisms (SNPs) in RNASET2 gene were determined with a Taqman probe on a Fluidigm EPl platform. Haplotypes and their frequencies were analyzed with a SHEsis online software. RESULTS: There was a significant difference in allele frequencies of rs3777722, rs3777723 and rs9355610 between the GD patients and the controls (P=0...
December 2013: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Patrick T Dolan, Chaoying Zhang, Sudip Khadka, Vaithilingaraja Arumugaswami, Abbey D Vangeloff, Nicholas S Heaton, Sudhir Sahasrabudhe, Glenn Randall, Ren Sun, Douglas J LaCount
Hepatitis C virus (HCV) alters the global behavior of the host cell to create an environment conducive to its own replication, but much remains unknown about how HCV proteins elicit these changes. Thus, a better understanding of the interface between the virus and host cell is required. Here we report the results of a large-scale yeast two-hybrid screen to identify protein-protein interactions between HCV genotype 2a (strain JFH1) and cellular factors. Our study identified 112 unique interactions between 7 HCV and 94 human proteins, over 40% of which have been linked to HCV infection by other studies...
December 2013: Molecular BioSystems
Suk-Kyun Yang, Myunghee Hong, Wanting Zhao, Yusun Jung, Jiwon Baek, Naeimeh Tayebi, Kyung Mo Kim, Byong Duk Ye, Kyung-Jo Kim, Sang Hyoung Park, Inchul Lee, Eun-Ju Lee, Won Ho Kim, Jae Hee Cheon, Young-Ho Kim, Byung Ik Jang, Hyun-Soo Kim, Jai Hyun Choi, Ja Seol Koo, Ji Hyun Lee, Sung-Ae Jung, Yeoun Joo Lee, Joo Young Jang, Hyoung Doo Shin, Daehee Kang, Hee-Shang Youn, Jianjun Liu, Kyuyoung Song
OBJECTIVE: Crohn's disease (CD) is an intractable inflammatory bowel disease (IBD) of unknown cause. Recent meta-analysis of the genome-wide association studies (GWAS) and Immunochip data identified 163 susceptibility loci to IBD in Caucasians, however there are limited studies in other populations. METHODS: We performed a GWAS and two validation studies in the Korean population comprising a total of 2311 patients with CD and 2442 controls. RESULTS: We confirmed four previously reported loci: TNFSF15, IL23R, the major histocompatibility complex region, and the RNASET2-FGFR1OP-CCR6 region...
January 2014: Gut
Francesco Acquati, Marta Lualdi, Sabrina Bertilaccio, Laura Monti, Giovanna Turconi, Marco Fabbri, Annalisa Grimaldi, Achille Anselmo, Antonio Inforzato, Angelo Collotta, Laura Cimetti, Cristina Riva, Laura Gribaldo, Paolo Ghia, Roberto Taramelli
In recent years, the role played by the stromal microenvironment has been given growing attention in order to achieve a full understanding of cancer initiation and progression. Because cancer is a tissue-based disease, the integrity of tissue architecture is a major constraint toward cancer growth. Indeed, a large contribution of the natural resistance to cancer stems from stromal microenvironment components, the dysregulation of which can facilitate cancer occurrence. For instance, recent experimental evidence has highlighted the involvement of stromal cells in ovarian carcinogenesis, as epitomized by ovarian xenografts obtained by a double KO of the murine Dicer and Pten genes...
May 14, 2013: Proceedings of the National Academy of Sciences of the United States of America
Chih-Ping Chen, Yi-Yung Chen, Schu-Rern Chern, Peih-Shan Wu, Jun-Wei Su, Yu-Ting Chen, Li-Feng Chen, Wayseen Wang
We present rapid aneuploidy diagnosis of de novo partial trisomy 12q (12q24.21→qter) and partial monosomy 6q (6q27→qter) by aCGH using uncultured amniocytes in a fetus with coarctation of the aorta, ventriculomegaly and thickened nuchal fold. We discuss the association of TBX3, TBX5 and MED13L gene duplication with coarctation of the aorta, and the association of RNASET2 gene haploinsufficiency with ventriculomegaly in this case.
March 1, 2013: Gene
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