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Lissania Guerra-Calderas, Rodrigo González-Barrios, Carlos César Patiño, Nicolás Alcaraz, Marisol Salgado-Albarrán, David Cantú de León, Clementina Castro Hernández, Yesennia Sánchez-Pérez, Héctor Aquiles Maldonado-Martínez, Inti A De la Rosa-Velazquez, Fernanda Vargas-Romero, Luis A Herrera, Alejandro García-Carrancá, Ernesto Soto-Reyes
Histone demethylase KDM4A is involved in H3K9me3 and H3K36me3 demethylation, which are epigenetic modifications associated with gene silencing and RNA Polymerase II elongation, respectively. KDM4A is abnormally expressed in cancer, affecting the expression of multiple targets, such as the CHD5 gene. This enzyme localizes at the first intron of CHD5 , and the dissociation of KDM4A increases gene expression. In vitro assays showed that KDM4A-mediated demethylation is enhanced in the presence of CTCF, suggesting that CTCF could increase its enzymatic activity in vivo, however the specific mechanism by which CTCF and KDM4A might be involved in the CHD5 gene repression is poorly understood...
March 30, 2018: Oncotarget
Xiaopeng Hu, Junping Ao, Xinyue Li, Huijuan Zhang, Ji Wu, Weiwei Cheng
Background: The etiology and pathogenesis of pre-eclampsia (PE) is unclear, and there is no ideal early clinical biomarker for prediction of PE. The competing endogenous RNA (ceRNA) hypothesis is a new approach to uncover the molecular pathology of PE. The first aim of this study was to perform messenger RNA, long non-coding RNA, and circular RNA (circRNA) expression profiling of human normal and severe pre-eclampsia (SPE) placentas. circRNA, which has a stable structure, is a more suitable biomarker than other types of RNA...
2018: Clinical Epigenetics
Xiao Zhu, Qingming Kong, Liwei Xie, Zhihong Chen, Hongmei Li, Zhu Zhu, Yongmei Huang, Feifei Lan, Haiqing Luo, Jingting Zhan, Hongrong Ding, Jinli Lei, Qin Xiao, Weiming Fu, Wenguo Fan, Jinfang Zhang, Hui Luo
Previous studies showed that the low expressions of chromodomain-helicase-DNA-binding protein 5 (CHD5) were intensively associated with deteriorative biologic and clinical characteristics as well as outcomes in many tumors. The aim of this study is to determine whether CHD5 single nucleotide polymorphisms (SNPs) contribute to the prognosis of hepatocellular carcima (HCC). The SNPs were selected according to their linkage disequilibrium (LD) in the targeted next-generation sequencing (NGS) and then genotyped with TaqMan probers...
March 2, 2018: Oncotarget
Jung Ran Choi, Sang-Baek Koh, Seong Yong Park, Hye Run Kim, Hyojin Lee, Dae Ryong Kang
Background: Lung cancer is the leading cause of cancer-related death worldwide, for which smoking is considered as the primary risk factor. The present study was conducted to determine whether genetic alterations induced by radon exposure are associated with the susceptible risk of lung cancer in never smokers. Methods: To accurately identify mutations within individual tumors, next generation sequencing was conduct for 19 pairs of lung cancer tissue. The associations of germline and somatic variations with radon exposure were visualized using OncoPrint and heatmap graphs...
December 2017: Journal of Cancer Prevention
Guangru Xu, Hongxing Zhu, Minghui Zhang, Jinhua Xu
Gastric cancer (GC) is the third leading cause of cancer-related mortality in China and worlwide; hence, the identification of GC-related genes is necessary for the development of effective treatment strategies. In this study, histone deacetylase 3 (HDAC3) was identified as the most significantly upregulated cancer-related gene in GC tissues by microarray. In accordance with this, HDAC3 expression was found to be upregulated in GC cell lines/tissues. Further experiments indicated that the knockdown of HDAC3 decreased GC cell viability, reduced the colony formation number and decreased tumor weight...
January 2018: International Journal of Molecular Medicine
Mi-Jin An, Chul-Hong Kim, Gyu-You Nam, Dae-Hyun Kim, Sangmyung Rhee, Sung-Jin Cho, Jung-Woong Kim
Throughout life, the human eye is continuously exposed to sunlight and artificial lighting. Ambient light exposure can lead to visual impairment and transient or permanent blindness. To mimic benign light stress conditions, Mus musculus eyes were exposed to low-energy UVB radiation, ensuring no severe morphological changes in the retinal structure post-exposure. We performed RNA-seq analysis to reveal the early transcriptional changes and key molecular pathways involved before the activation of the canonical cell death pathway...
January 2018: Environmental Toxicology
M T Pisansky, A E Young, M B O'Connor, I I Gottesman, A Bagchi, J C Gewirtz
Although autism spectrum disorders (ASDs) share a core set of nosological features, they exhibit substantial genetic heterogeneity. A parsimonious hypothesis posits that dysregulated epigenetic mechanisms represent common pathways in the etiology of ASDs. To investigate this hypothesis, we generated a novel mouse model resulting from brain-specific deletion of chromodomain helicase DNA-binding 5 (Chd5), a chromatin remodeling protein known to regulate neuronal differentiation and a member of a gene family strongly implicated in ASDs...
June 13, 2017: Translational Psychiatry
Onur Baykara, Merve Tansarikaya, Pelin Bulut, Ahmet Demirkaya, Nur Buyru
Lung cancer is one of the deadliest types of cancers and genetic and epigenetic alterations play major roles in its development. Chromodomain (CHD) protein family acts in chromatin organization, regulation of transcription and also genomic stability and cancer prevention. Although CHD5, a member of this family was shown to contribute to major cellular events and functions as a tumor suppressor gene in various types of cancer, it is not clear whether CHD5 plays a role in lung carcinogenesis. The aim of this study was to investigate the possible role of CHD5 in progression of non-small cell lung cancer (NSCLC)...
June 30, 2017: Gene
Zhongliang Ma, Jinlian Song, Simin Liu, Linlin Han, Yangping Chen, Yaqiu Wang, Chundong Yu, Lin Hou
Chromodomain helicase DNA binding protein 5 (CHD5) has been identified as a tumor suppressor in mouse models. Downregulation of CHD5 gene expression is frequently observed in breast cancer cells and tissues. This may be explained by deletions or other mutations; however, alternative mechanisms require investigation. Therefore, the present study evaluated whether CHD5 aberrant methylation has a role in primary breast tumors. A total of 389 patients with primary breast cancer (including 252 paraffin-embedded specimens and 137 fresh-frozen samples) were enrolled in the present study...
November 2016: Oncology Letters
Justyna Nitarska, Jacob G Smith, William T Sherlock, Michele M G Hillege, Alexi Nott, William D Barshop, Ajay A Vashisht, James A Wohlschlegel, Richard Mitter, Antonella Riccio
Histone modifications and chromatin remodeling represent universal mechanisms by which cells adapt their transcriptional response to rapidly changing environmental conditions. Extensive chromatin remodeling takes place during neuronal development, allowing the transition of pluripotent cells into differentiated neurons. Here, we report that the NuRD complex, which couples ATP-dependent chromatin remodeling with histone deacetylase activity, regulates mouse brain development. Subunit exchange of CHDs, the core ATPase subunits of the NuRD complex, is required for distinct aspects of cortical development...
November 1, 2016: Cell Reports
Raul Elgueta, Dan Tse, Sophie J Deharvengt, Marcus R Luciano, Catherine Carriere, Randolph J Noelle, Radu V Stan
Plasmalemma vesicle-associated protein (Plvap) is an endothelial protein with roles in endothelial diaphragm formation and maintenance of basal vascular permeability. At the same time, Plvap has roles in immunity by facilitating leukocyte diapedesis at inflammatory sites and controlling peripheral lymph node morphogenesis and the entry of soluble Ags into lymph node conduits. Based on its postulated role in diapedesis, we have investigated the role of Plvap in hematopoiesis and show that deletion of Plvap results in a dramatic decrease of IgM+ IgDlo B cells in both the spleen and the peritoneal cavity...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Cees Bm Oudejans, Ankie Poutsma, Omar J Michel, Hari K Thulluru, Joyce Mulders, Henri J van de Vrugt, Erik A Sistermans, Marie van Dijk
The familial forms of early onset pre-eclampsia and related syndromes (HELLP) present with hypertension and proteinuria in the mother and growth restriction of the fetus. Genetically, these clinically similar entities are caused by different founder-dependent, placentally-expressed paralogous genes. All susceptibility genes (STOX1, lincHELLP, INO80B) identified so far are master control genes that regulate an essential trophoblast differentiation pathway, but act at different entry points. Many genes remain to be identified...
2016: Scientific Reports
Xiaofeng Sun, Dajiang Xiao, Ting Xu, Yuan Yuan
AIM: To investigate the role of miR-24-3p in tumorigenesis and chemosensitivity in head and neck squamous cell carcinoma (HNSCC). METHODS: Growth rate and colony formation assays were performed after transfection with miR-24-3p mimic and inhibitor in cultured SCC-15 cells, followed by a CellTiter-Glo(®) assay. Western blot and luciferase assays were performed to investigate the direct target of miR-24-3p. Xenograft mouse model was used to evaluate combinatorial effects of miR-24-3p inhibitor and 5-fluorouracil...
December 2016: Future Oncology
Alexandra Wille, Thomas Amort, Nicolas Singewald, Simone B Sartori, Alexandra Lusser
Enhanced anxiety is a salient feature of a number of psychiatric disorders including anxiety disorders, trauma-related disorders and depression. Although aberrant expression of various genes has been detected in patients suffering from persistent high anxiety as well as in high anxiety rodent models, the molecular mechanisms responsible for altered transcription regulation have been poorly addressed. Transcription regulation intimately involves the contribution of chromatin modifying processes, such as histone modification and ATP-dependent chromatin remodeling, yet their role in pathological anxiety is not known...
September 15, 2016: Behavioural Brain Research
Zhenfang Du, Lili Li, Xin Huang, Jie Jin, Suming Huang, Qian Zhang, Qian Tao
Renal cell carcinoma (RCC) is the most common urological cancer with steadily increasing incidence. A series of tumor suppressor genes (TSGs) have been identified methylated in RCC as potential epigenetic biomarkers. We identified a 1p36.3 TSG candidate CHD5 as a methylated target in RCC through epigenome study. As the role of CHD5 in RCC pathogenesis remains elusive, we further studied its expression and molecular functions in RCC cells. We found that CHD5 was broadly expressed in most normal genitourinary tissues including kidney, but frequently silenced or downregulated by promoter CpG methylation in 78% of RCC cell lines and 44% (24/55) of primary tumors...
April 19, 2016: Oncotarget
Koumudi Naraparaju, Venkatadri Kolla, Tiangang Zhuang, Mayumi Higashi, Radhika Iyer, Sriharsha Kolla, Erin R Okawa, Gerd A Blobel, Garrett M Brodeur
Neuroblastoma (NB), a tumor of the sympathetic nervous system, is the most common extracranial solid tumor of childhood. We and others have identified distinct patterns of genomic change that underlie diverse clinical behaviors, from spontaneous regression to relentless progression. We first identified CHD5 as a tumor suppressor gene that is frequently deleted in NBs. Mutation of the remaining CHD5 allele is rare in these tumors, yet expression is very low or absent, so expression is likely regulated by epigenetic mechanisms...
March 29, 2016: Oncotarget
Denis Kusevic, Srikanth Kudithipudi, Albert Jeltsch
Bacterial HEMK2 homologs initially had been proposed to be involved in heme biogenesis or to function as adenine DNA methyltransferase. Later it was shown that this family of enzymes has protein glutamine methyltransferase activity, and they methylate the glutamine residue in the GGQ motif of ribosomal translation termination factors. The murine HEMK2 enzyme methylates Gln(185) of the eukaryotic translation termination factor eRF1. We have employed peptide array libraries to investigate the peptide sequence recognition specificity of murine HEMK2...
March 18, 2016: Journal of Biological Chemistry
Alexandra Wille, Verena Maurer, Paolo Piatti, Nigel Whittle, Dietmar Rieder, Nicolas Singewald, Alexandra Lusser
Successful attenuation of fearful memories is a cognitive process requiring initiation of highly coordinated transcription programs. Chromatin-modulating mechanisms such as DNA methylation and histone modifications, including acetylation, are key regulators of these processes. However, knowledge concerning the role of ATP-dependent chromatin remodeling factors (ChRFs) being required for successful fear extinction is lacking. Underscoring the potential importance of these factors that alter histone-DNA contacts within nucleosomes are recent genome-wide association studies linking several ChRFs to various human cognitive and psychiatric disorders...
2015: Frontiers in Behavioral Neuroscience
Song Wu, Zhao Yang, Rui Ye, Dan An, Chong Li, Yitian Wang, Yongqiang Wang, Yi Huang, Huan Liu, Feida Li, Luyun He, Da Sun, Yuan Yu, Qiaoling Li, Peide Huang, Meng Zhang, Xin Zhao, Tengteng Bi, Xuehan Zhuang, Liyan Zhang, Jingxiao Lu, Xiaojuan Sun, Fangjian Zhou, Chunxiao Liu, Guosheng Yang, Yong Hou, Zusen Fan, Zhiming Cai
Bladder cancer (BC) is distinguished by high rate of recurrence after surgery, but the underlying mechanisms remain poorly understood. Here we performed the whole-exome sequencing of 37 BC individuals including 20 primary and 17 recurrent samples in which the primary and recurrent samples were not from the same patient. We uncovered that MLL, EP400, PRDM2, ANK3 and CHD5 exclusively altered in recurrent BCs. Specifically, the recurrent BCs and bladder cancer cells with MLL mutation displayed increased histone H3 tri-methyl K4 (H3K4me3) modification in tissue and cell levels and showed enhanced expression of GATA4 and ETS1 downstream...
January 19, 2016: Oncotarget
Isabelle Westerlund, Ulrika Nyman, Johan Holmberg
No abstract text is available yet for this article.
December 2015: International Journal of Developmental Neuroscience
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