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Zhibin Cui, Yingjia Shen, Kenny H Chen, Suresh K Mittal, Jer-Yen Yang, GuangJun Zhang
No abstract text is available yet for this article.
April 24, 2017: Scientific Reports
Shixin Ma, Xiaoling Wan, Zihou Deng, Lei Shi, Congfang Hao, Zhenyuan Zhou, Chun Zhou, Yiyuan Fang, Jinghua Liu, Jing Yang, Xia Chen, Tiantian Li, Aiping Zang, Shigang Yin, Bin Li, Joel Plumas, Laurence Chaperot, Xiaoming Zhang, Guoliang Xu, Lubin Jiang, Nan Shen, Sidong Xiong, Xiaoming Gao, Yan Zhang, Hui Xiao
TLR7/9 signals are capable of mounting massive interferon (IFN) response in plasmacytoid dendritic cells (pDCs) immediately after viral infection, yet the involvement of epigenetic regulation in this process has not been documented. Here, we report that zinc finger CXXC family epigenetic regulator CXXC5 is highly expressed in pDCs, where it plays a crucial role in TLR7/9- and virus-induced IFN response. Notably, genetic ablation of CXXC5 resulted in aberrant methylation of the CpG-containing island (CGI) within the Irf7 gene and impaired IRF7 expression in steady-state pDCs...
April 17, 2017: Journal of Experimental Medicine
Weiguo Sui, Zhoufang Shi, Wen Xue, Minglin Ou, Ying Zhu, Jiejing Chen, Hua Lin, Fuhua Liu, Yong Dai
The aim of the present study was to screen gastric cancer (GC) tissue and adjacent tissue for differences in mRNA and circular (circRNA) expression, to analyze the differences in circRNA and mRNA expression, and to investigate the circRNA expression in gastric carcinoma and its mechanism. circRNA and mRNA differential expression profiles generated using Agilent microarray technology were analyzed in the GC tissues and adjacent tissues. qRT-PCR was used to verify the differential expression of circRNAs and mRNAs according to the interactions between circRNAs and miRNAs as well as the possible existence of miRNA and mRNA interactions...
March 2017: Oncology Reports
Zhibin Cui, Yingjia Shen, Kenny H Chen, Suresh K Mittal, Jer-Yen Yang, GuangJun Zhang
Malignant peripheral nerve sheath tumors (MPNSTs) are a type of rare sarcomas with a poor prognosis due to its highly invasive nature and limited treatment options. Currently there is no targeted-cancer therapy for this type of malignancy. Thus, it is important to identify more cancer driver genes that may serve as targets of cancer therapy. Through comparative oncogenomics, we have found that KANK1 was a candidate tumor suppressor gene (TSG) for human MPNSTs. Although KANK1 is known as a cytoskeleton regulator, its tumorigenic function in MPNSTs remains largely unknown...
January 9, 2017: Scientific Reports
Inhwan Lee, Sooho Choi, Ji-Hye Yun, Seol Hwa Seo, Sehee Choi, Kang-Yell Choi, Weontae Lee
Dishevelled (Dvl) plays a crucial role in Wnt signaling by interacting with membrane-bound receptors and downstream molecules through its PDZ domain. CXXC5 is one of the key molecules that interacts with Dvl and negatively regulates the Wnt/β-catenin pathway in osteoblast differentiation. Recently, the Dvl-CXXC5 interaction has been identified as an excellent target for osteoporosis treatment. Therefore, it is desirable to have detailed structural information for the Dvl-CXXC5 interaction. Although solution structures of the Dvl1 PDZ domain have been reported, a high-resolution crystal structure would provide detailed sidechain information that is essential for drug development...
April 8, 2017: Biochemical and Biophysical Research Communications
Pelin Yaşar, Gamze Ayaz, Mesut Muyan
17β-estradiol (E2), the primary circulating estrogen hormone, mediates physiological and pathophysiological functions of breast tissue mainly through estrogen receptor α (ERα). Upon binding to E2, ERα modulates the expression of target genes involved in the regulation of cellular proliferation primarily through interactions with specific DNA sequences, estrogen response elements (EREs). Our previous microarray results suggested that E2-ERα modulates CXXC5 expression. Because of the presence of a zinc-finger CXXC domain (ZF-CXXC), CXXC5 is considered to be a member of the ZF-CXXC family, which binds to non-methylated CpG dinucleotides...
November 25, 2016: Scientific Reports
Xiyang Peng, Guanming Li, Yuequn Wang, Jian Zhuang, Rong Luo, Jimei Chen, Fa Chen, Yan Shi, Jiani Li, Zuoqiong Zhou, Xiaoyang Mo, Xianchu Liu, Wuzhou Yuan, Qun Zeng, Yongqing Li, Zhigang Jiang, Yongqi Wan, Xiangli Ye, Wei Xu, Xijun Wang, Xiongwei Fan, Ping Zhu, Xiushan Wu, Yun Deng
BACKGROUND: CXXC-type zinc-finger protein CXXC5 has been reported to be associated with the development of cardiovascular disease. Recently, through signaling pathway screening we found that CXXC5 activated Tgfβ and myocardial differentiation signaling pathways simultaneously. Although the physiological and pathological function of CXXC5 in many organs has been well elucidated, its function in heart remains unclear. METHODS AND RESULTS: Here, we found that zebrafish CXXC5 and SMAD were interacting through ZF-CXXC and MH1 domain...
July 1, 2016: International Journal of Cardiology
Angela Stoddart, Zhijian Qian, Anthony A Fernald, Rachel J Bergerson, Jianghong Wang, Theodore Karrison, John Anastasi, Elizabeth T Bartom, Aaron L Sarver, Megan E McNerney, David A Largaespada, Michelle M Le Beau
No abstract text is available yet for this article.
June 2016: Haematologica
Hyun-Yi Kim, Sehee Choi, Ji-Hye Yoon, Hwan Jung Lim, Hyuk Lee, Jiwon Choi, Eun Ji Ro, Jung-Nyoung Heo, Weontae Lee, Kyoung Tai No, Kang-Yell Choi
Bone anabolic agents promoting bone formation and rebuilding damaged bones would ideally overcome the limitations of anti-resorptive therapy, the current standard prescription for osteoporosis. However, the currently prescribed parathyroid hormone (PTH)-based anabolic drugs present limitations and adverse effects including osteosarcoma during long-term use. Also, the antibody-based anabolic drugs that are currently being developed present the potential limits in clinical application typical of macromolecule drugs...
April 1, 2016: EMBO Molecular Medicine
Alfonso Bettin, Ismael Reyes, Niradiz Reyes
BACKGROUND: The aim of this study was to evaluate the gene expression profiles of a set of prostate cancer-associated genes in prostate cancer cell lines, to determine their association with different cancer phenotypes and identify potential novel biomarkers for this disease. METHODS: Quantitative real-time PCR was used to determine the expression profiles of 21 prostate cancer-associated genes in the human prostate cancer cell lines PC-3 and LNCaP, using the nontumorigenic cell line PWR-1E as control cell line...
May 28, 2016: International Journal of Biological Markers
Mi-Yeon Kim, Hyun-Yi Kim, Jiso Hong, Daesoo Kim, Hyojung Lee, Eunji Cheong, Yangsin Lee, Jürgen Roth, Dong Goo Kim, Do Sik Min, Kang-Yell Choi
Myelination in corpus callosum plays important role for normal brain functions by transferring neurological information between various brain regions. However, the factors controlling expression of myelin genes in myelination are poorly understood. Here, CXXC5, a recently identified protein with CXXC-type zinc finger DNA binding motif, was characterized as a transcriptional activator of major myelin genes. We identified expression of CXXC5 expression was increased by Wnt/β-catenin signaling. CXXC5 specifically expressed in the white matter induced expression of myelin genes through the direct binding of CXXC DNA-binding motif of CXXC5 on the MBP promoter...
March 2016: Glia
Saara Marttila, Laura Kananen, Juulia Jylhävä, Tapio Nevalainen, Antti Hervonen, Marja Jylhä, Mikko Hurme
The heritability of lifespan is 20-30%, but only a few genes associated with longevity have been identified. To explain this discrepancy, the inheritance of epigenetic features, such as DNA methylation, have been proposed to contribute to the heritability of lifespan.We investigated whether parental lifespan is associated with DNA methylation profile in nonagenarians. A regression model, adjusted for differences in blood cell proportions, identified 659 CpG sites where the level of methylation was associated with paternal lifespan...
October 13, 2015: Oncotarget
Soung-Hoon Lee, Mi-Yeon Kim, Hyun-Yi Kim, Young-Mi Lee, Heesu Kim, Kyoung Ae Nam, Mi Ryung Roh, Do Sik Min, Kee Yang Chung, Kang-Yell Choi
Wnt/β-catenin signaling plays important roles in cutaneous wound healing and dermal fibrosis. However, its regulatory mechanism has not been fully elucidated, and a commercially available wound-healing agent targeting this pathway is desirable but currently unavailable. We found that CXXC-type zinc finger protein 5 (CXXC5) serves as a negative feedback regulator of the Wnt/β-catenin pathway by interacting with the Dishevelled (Dvl) protein. In humans, CXXC5 protein levels were reduced in epidermal keratinocytes and dermal fibroblasts of acute wounds...
June 29, 2015: Journal of Experimental Medicine
Andrea Kühnl, Peter J M Valk, Mathijs A Sanders, Adam Ivey, Robert K Hills, Ken I Mills, Rosemary E Gale, Martin F Kaiser, Richard Dillon, Melanie Joannides, Amanda Gilkes, Torsten Haferlach, Susanne Schnittger, Estelle Duprez, David C Linch, Ruud Delwel, Bob Löwenberg, Claudia D Baldus, Ellen Solomon, Alan K Burnett, David Grimwade
The gene CXXC5 on 5q31 is frequently deleted in acute myeloid leukemia (AML) with del(5q), suggesting that inactivation of CXXC5 might play a role in leukemogenesis. Here, we investigated the functional and prognostic implications of CXXC5 expression in AML. CXXC5 mRNA was downregulated in AML with MLL rearrangements, t(8;21) and GATA2 mutations. As a mechanism of CXXC5 inactivation, we found evidence for epigenetic silencing by promoter methylation. Patients with CXXC5 expression below the median level had a lower relapse rate (45% vs 59%; P = ...
May 7, 2015: Blood
H-Y Kim, J-Y Yoon, J-H Yun, K-W Cho, S-H Lee, Y-M Rhee, H-S Jung, H J Lim, H Lee, J Choi, J-N Heo, W Lee, K T No, D Min, K-Y Choi
The positive roles of the Wnt/β-catenin pathway in osteoblast differentiation and bone mineral density (BMD) maintenance have been clearly demonstrated in both animal experiments and clinical investigations. CXXC finger protein 5 (CXXC5), a recently identified negative regulator of the Wnt/β-catenin pathway, showed altered cellular localization and function, which were dependent on the cell type in previous studies. However, the in vivo function of CXXC5 has not been clearly investigated yet. Here, we characterized CXXC5 as a negative regulator of osteoblast differentiation and bone formation...
June 2015: Cell Death and Differentiation
Øystein Bruserud, Håkon Reikvam, Hanne Fredly, Jørn Skavland, Karen-Marie Hagen, Tuyen Thy van Hoang, Annette K Brenner, Amir Kadi, Audrey Astori, Bjørn Tore Gjertsen, Frederic Pendino
The CXXC5 gene encodes a transcriptional activator with a zinc-finger domain, and high expression in human acute myeloid leukemia (AML) cells is associated with adverse prognosis. We now characterized the biological context of CXXC5 expression in primary human AML cells. The global gene expression profile of AML cells derived from 48 consecutive patients was analyzed; cells with high and low CXXC5 expression then showed major differences with regard to extracellular communication and intracellular signaling...
February 20, 2015: Oncotarget
Guangming Li, Xiangli Ye, Xiyang Peng, Yun Deng, Wuzhou Yuan, Yongqing Li, Xiaoyang Mo, Xijun Wang, Yongqi Wan, Xianchu Liu, Tingfang Chen, Zhigang Jiang, Xiongwei Fan, Xiushan Wu, Yuequn Wang
CXXC5 is a member of the CXXC-type zinc-finger domain containing protein family, which is suggested to function in gene transcription, cell adhesion and cytoskeleton organization. Previous studies have revealed that CXXC5 is expressed in skeletal muscle, but whether it regulates skeletal myogenesis is yet unknown. Here, we screened for the possible signaling pathways in which CXXC5 might participate using luciferase gene reporters. The results indicated that CXXC5 significantly increased the activities of the promoters of genes involved in skeletal muscle differentiation...
December 2014: Journal of Muscle Research and Cell Motility
Hyun-Yi Kim, Dong-Hwa Yang, Song-Weon Shin, Mi-Yeon Kim, Jae-Hyun Yoon, Suhyun Kim, Hae-Chul Park, Dong Woo Kang, Dosik Min, Man-Wook Hur, Kang-Yell Choi
CXXC5 is a member of a small subset of proteins containing CXXC-type zinc-finger domain. Here, we show that CXXC5 is a transcription factor activating Flk-1, a receptor for vascular endothelial growth factor. CXXC5 and Flk-1 were accumulated in nucli and membrane of mouse embryonic stem cells (mESCs), respectively, during their endothelial differentiation. CXXC5 overexpression induced Flk-1 transcription in both endothelium-differentiated mESCs and human umbilical vein endothelial cells (HUVECs). In vitro DNA binding assay showed direct interaction of CXXC5 on the Flk-1 promoter region, and mutation on its DNA-binding motif abolished transcriptional activity...
February 2014: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Audrey Astori, Hanne Fredly, Thomas Aquinas Aloysius, Lars Bullinger, Véronique Mansat-De Mas, Pierre de la Grange, François Delhommeau, Karen Marie Hagen, Christian Récher, Isabelle Dusanter-Fourt, Stian Knappskog, Johan Richard Lillehaug, Frédéric Pendino, Øystein Bruserud
The retinoid-responsive gene CXXC5 localizes to the 5q31.2 chromosomal region and encodes a retinoid-inducible nuclear factor (RINF) that seems important during normal myelopoiesis. We investigated CXXC5/RINF expression in primary human acute myeloid leukemia (AML) cells derived from 594 patients, and a wide variation in CXXC5/RINF mRNA levels was observed both in the immature leukemic myeloblasts and in immature acute lymphoblastic leukemia cells. Furthermore, patients with low-risk cytogenetic abnormalities showed significantly lower levels compared to patients with high-risk abnormalities, and high RINF/CXXC5/ mRNA levels were associated with decreased overall survival for patients receiving intensive chemotherapy for newly diagnosed AML...
September 2013: Oncotarget
X Wang, P Liao, X Fan, Y Wan, Y Wang, Y Li, Z Jiang, X Ye, X Mo, K Ocorr, Y Deng, X Wu, W Yuan
Apoptosis is a widespread phenomenon and its dysregulation may result in a variety of human pathologies, such as cancer, autoimmune diseases and neurodegenerative disorders. CXXC-type zinc finger protein 5 (CXXC5) is commonly considered as a tumor suppressor undergoing deregulation or deletion in hematonosis. But it has implied involvement in apoptosis indirectly and the molecular mechanism remains unknown. In this study, we investigated CXXC5-induced apoptosis as well as its underlying mechanism. A fluorescence resonance energy transfer (FRET) assay suggested that CXXC5 induced cell death and caspase-3 activity in primary rat cortical neurons...
September 2013: Current Molecular Medicine
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