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Geoffrey Liu, Sinead Cuffe, Shermi Liang, Abul K Azad, Lu Cheng, Yonathan Brhane, Xin Qiu, David W Cescon, Jeff P Bruce, Zhuo Chen, Dangxiao Cheng, Devalben Patel, Brandon C Tse, Scott A Laurie, Glenwood D Goss, Natasha B Leighl, Rayjean J Hung, Penelope A Bradbury, Lesley Seymour, Frances A Shepherd, Ming-Sound Tsao, Bingshu E Chen, Wei Xu, David Reisman
PURPOSE: BRM, a key catalytic subunit of the SWI/SNF chromatin remodeling complex, is a putative tumor susceptibility gene that is silenced in 15% of non-small cell lung cancer (NSCLC). Two novel BRM promoter polymorphisms (BRM-741, BRM-1321) are associated with reversible epigenetic silencing of BRM protein expression. EXPERIMENTAL DESIGN: Advanced NSCLC patients from the Princess Margaret (PM) cohort study and from the CCTG BR.24 clinical trial were genotyped for BRM promoter polymorphisms...
November 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Zhaohui Gu, Michelle Churchman, Kathryn Roberts, Yongjin Li, Yu Liu, Richard C Harvey, Kelly McCastlain, Shalini C Reshmi, Debbie Payne-Turner, Ilaria Iacobucci, Ying Shao, I-Ming Chen, Marcus Valentine, Deqing Pei, Karen L Mungall, Andrew J Mungall, Yussanne Ma, Richard Moore, Marco Marra, Eileen Stonerock, Julie M Gastier-Foster, Meenakshi Devidas, Yunfeng Dai, Brent Wood, Michael Borowitz, Eric E Larsen, Kelly Maloney, Leonard A Mattano, Anne Angiolillo, Wanda L Salzer, Michael J Burke, Francesca Gianni, Orietta Spinelli, Jerald P Radich, Mark D Minden, Anthony V Moorman, Bella Patel, Adele K Fielding, Jacob M Rowe, Selina M Luger, Ravi Bhatia, Ibrahim Aldoss, Stephen J Forman, Jessica Kohlschmidt, Krzysztof Mrózek, Guido Marcucci, Clara D Bloomfield, Wendy Stock, Steven Kornblau, Hagop M Kantarjian, Marina Konopleva, Elisabeth Paietta, Cheryl L Willman, Mignon L Loh, Stephen P Hunger, Charles G Mullighan
Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5...
November 8, 2016: Nature Communications
Qi-Shan Zhang, Yuan-Gao Liao, Zhong Ji, Yong Gu, Hai-Shan Jiang, Zuo-Shan Xie, Su-Yue Pan, Ya-Fang Hu
The present study aimed to investigate the protective effect of a modified p5 peptide, TFP5, on 1-methyl-4-phenyl pyridine ion (MPP(+))-induced neurotoxicity in cortical neurons and explore the therapeutic effect of TFP5 on Parkinson's disease (PD). MPP(+) was applied to a primary culture of mouse cortical neurons to establish the cell model of PD. Neurons were divided into four groups: Control, model (MPP(+)), scrambled peptide (Scb) (Scb + MPP(+)) and TFP5 (TFP5 + MPP(+)) groups. Pretreatment with Scb or TFP5 was applied to the latter two groups, respectively, for 3 h, while phosphate-buffered saline was applied to the control and model groups...
October 2016: Experimental and Therapeutic Medicine
Kyogo Suzuki, Yusuke Okuno, Nozomu Kawashima, Hideki Muramatsu, Tatsuya Okuno, Xinan Wang, Shinsuke Kataoka, Yuko Sekiya, Motoharu Hamada, Norihiro Murakami, Daiei Kojima, Kotaro Narita, Atsushi Narita, Hirotoshi Sakaguchi, Kimiyoshi Sakaguchi, Nao Yoshida, Nobuhiro Nishio, Asahito Hama, Yoshiyuki Takahashi, Kazuko Kudo, Koji Kato, Seiji Kojima
PURPOSE: Acute lymphoblastic leukemia (ALL) makes up a significant proportion of all pediatric cancers, and relapsed ALL is a leading cause of cancer-associated deaths in children. Identification of risk factors and druggable molecular targets in ALL can lead to a better stratification of treatments and subsequent improvement in prognosis. PATIENTS AND METHODS: We enrolled 59 children with relapsed or primary refractory ALL who were treated in our institutions. We primarily performed RNA sequencing (RNA-seq) using patients' leukemic cells to comprehensively detect gene fusions and analyze gene expression profiles...
October 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Barry H Smith, Tapan Parikh, Zoe P Andrada, Thomas J Fahey, Nathaniel Berman, Madeline Wiles, Angelica Nazarian, Joanne Thomas, Anna Arreglado, Eugene Akahoho, David J Wolf, Daniel M Levine, Thomas S Parker, Lawrence S Gazda, Allyson J Ocean
PURPOSE: Agarose macrobeads containing mouse renal adenocarcinoma cells (RMBs) release factors, suppressing the growth of cancer cells and prolonging survival in spontaneous or induced tumor animals, mediated, in part, by increased levels of myocyte-enhancing factor (MEF2D) via EGFR-and AKT-signaling pathways. The primary objective of this study was to determine the safety of RMBs in advanced, treatment-resistant metastatic cancers, and then its efficacy (survival), which is the secondary objective...
2016: Cancer Growth and Metastasis
Maja Segedi, Laura N Anderson, Osvaldo Espin-Garcia, Ayelet Borgida, Teresa Bianco, Dangxiao Cheng, Zhuo Chen, Devalben Patel, M Catherine Brown, Wei Xu, David Reisman, Steven Gallinger, Michelle Cotterchio, Rayjean Hung, Geoffrey Liu, Sean P Cleary
Variant alleles of two promoter polymorphisms in the BRM gene (BRM-741, BRM-1321), create MEF2D transcription binding sites that lead to epigenetic silencing of BRM, the key catalytic component of the SWI/SNF chromatin remodeling complex. BRM suppression can be reversed pharmacologically.(1) Our group and others have reported associations with lung, head and neck, hepatocellular cancer risk,(1-3) and with lung and esophageal cancer prognosis (ASCO 2013; abstract 11057 & 4077). Herein, we assessed risk and survival associations with pancreatic cancer...
December 1, 2016: International Journal of Cancer. Journal International du Cancer
Liping Huang, Minzhen Deng, Yuping He, Shiyao Lu, Shu Liu, Yongqi Fang
Inactive myocyte enhancer factor 2D (MEF2D) and alpha-synuclein (α-syn) aggregation will cause neuronal death. MEF2D or α-syn degradation is also associated with macroautophagy, chaperone-mediated autophagy (CMA) and heat-shock protein 70 (HSP70). We found that β-asarone had positive effects on treating 6-hydroxydopamine (6-OHDA)-induced rats, but mechanisms of β-asarone affecting on MEF2D and α-syn via regulating the HSP70/MAPK/MEF2D/Beclin-1 pathway remain unclear. Unilateral 6-OHDA injection into the medial forebrain bundle was used to create PD rats, which were divided into four groups and administered for 30days: 6-OHDA model group, MEF2D inhibitor-treated group (SB203580, 0...
October 15, 2016: Behavioural Brain Research
Yuan-Fang Liu, Bai-Yan Wang, Wei-Na Zhang, Jin-Yan Huang, Ben-Shang Li, Ming Zhang, Lu Jiang, Jian-Feng Li, Ming-Jie Wang, Yu-Jun Dai, Zi-Guan Zhang, Qiang Wang, Jie Kong, Bing Chen, Yong-Mei Zhu, Xiang-Qin Weng, Zhi-Xiang Shen, Jun-Min Li, Jin Wang, Xiao-Jing Yan, Yan Li, Ying-Min Liang, Li Liu, Xie-Qun Chen, Wang-Gang Zhang, Jin-Song Yan, Jian-Da Hu, Shu-Hong Shen, Jing Chen, Long-Jun Gu, Deqing Pei, Yongjin Li, Gang Wu, Xin Zhou, Rui-Bao Ren, Cheng Cheng, Jun J Yang, Kan-Kan Wang, Sheng-Yue Wang, Jinghui Zhang, Jian-Qing Mi, Ching-Hon Pui, Jing-Yan Tang, Zhu Chen, Sai-Juan Chen
Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) were investigated using next-generation sequencing and copy number alteration analysis. Recurrent gene mutations and fusions were tested in an additional 87 adult and 93 pediatric patients. Among the 29 newly identified in-frame gene fusions, those involving MEF2D and ZNF384 were clinically relevant and were demonstrated to perturb B-cell differentiation, with EP300-ZNF384 inducing leukemia in mice. Eight gene expression subgroups associated with characteristic genetic abnormalities were identified, including leukemia with MEF2D and ZNF384 fusions in two distinct clusters...
June 2016: EBioMedicine
Zi-Jun Wang, Jennifer A Martin, Lauren E Mueller, Aaron Caccamise, Craig T Werner, Rachael L Neve, Amy M Gancarz, Jun-Xu Li, David M Dietz
BACKGROUND: Drug addiction is defined as a chronic disease characterized by compulsive drug seeking and episodes of relapse despite prolonged periods of drug abstinence. Neurobiological adaptations, including transcriptional and epigenetic alterations in the nucleus accumbens, are thought to contribute to this life-long disease state. We previously demonstrated that the transcription factor SMAD3 is increased after 7 days of withdrawal from cocaine self-administration. However, it is still unknown which additional factors participate in the process of chromatin remodeling and facilitate the binding of SMAD3 to promoter regions of target genes...
November 1, 2016: Biological Psychiatry
Ruixin Yang, Guodong Gao, Zixu Mao, Qian Yang
Parkinson's disease (PD), a complex neurodegenerative disorder, is pathologically characterized by the formation of Lewy bodies and loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Mitochondrial dysfunction is considered to be one of the most important causative mechanisms. In addition, dysfunction of chaperone-mediated autophagy (CMA), one of the lysosomal proteolytic pathways, has been shown to play an important role in the pathogenesis of PD. An exciting and important development is recent finding that CMA and mitochondrial quality control may be linked...
2016: Parkinson's Disease
Li Su, Yongli Luo, Zhi Yang, Jing Yang, Chao Yao, Feifei Cheng, Juanjuan Shan, Jun Chen, Fangfang Li, Limei Liu, Chungang Liu, Yanmin Xu, Lupin Jiang, Deyu Guo, Jesus Prieto, Matías A Ávila, Junjie Shen, Cheng Qian
Epithelial-mesenchymal transition (EMT) is an essential mechanism of metastasis, including in colorectal cancer. Although EMT processes are often triggered in cancer cells by their surrounding microenvironment, how EMT-relevant genes control these processes is not well understood. In multiple types of cancers, the transcription factor MEF2D has been implicated in cell proliferation, but its contributions to metastasis have not been addressed. Here, we show MEF2D is overexpressed in clinical colorectal cancer tissues where its high expression correlates with metastatic process...
September 1, 2016: Cancer Research
Shengquan Hu, Liang Wang, Shinghung Mak, Zaijun Zhang, Daping Xu, Haitao Li, Yide Li, Yuanjia Hu, Simon Ming Yuen Lee, Yuqiang Wang, Yifan Han
Danshensu (DSS) and tetramethylpyrazine (TMP) are active ingredients of Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort that are widely used in oriental medicine. Structural combination of compounds with known biological activity may lead to the formation of a molecule with multiple properties or new function profile. In the current study, the neuroprotective effects of DT-010, a novel analogue in which TMP was coupled to DSS through an ester bond and two allyl groups at the carboxyl group, were evaluated in a cellular model of Parkinson's disease (PD)...
December 2016: Neuromolecular Medicine
Baojian Guo, Chengyou Zheng, Wei Cai, Jiehong Cheng, Hongyu Wang, Haitao Li, Yewei Sun, Wei Cui, Yuqiang Wang, Yifan Han, Simon Ming-Yuen Lee, Zaijun Zhang
Chrysin, a flavonoid compound existing in several plants, is applied as a dietary supplement because of its beneficial effects on general human health and alleviation of neurological disorders. However, mechanisms underlying neuroprotection of chrysin has not been fully elucidated, and the effects of chrysin on the Parkinson's disease (PD) model in vivo have not been investigated. It is here shown that chrysin protects primary granular neurons against 1-methyl-4-phenylpyridinium ion insult via antiapoptosis by reversing the dysregulated expression of Bcl-2, Bax, and caspase 3...
July 6, 2016: Journal of Agricultural and Food Chemistry
Youzhu Qiu, Jie Yang, Shizhu Bian, Guozhu Chen, Jie Yu
Peroxisome proliferator-activated receptor gamma (PPARγ), a multiple functional transcription factor, has been reported to have anti-tumor effects through inhibition of cells proliferation. However, its effects on cardiac myxoma (CM) cells and the underlying signaling mechanism is unclear. In the present study, we demonstrated that the level of PPARγ is inversely correlated with that of myocyte enhancer factor 2D (MEF2D), a biomarker of CM. We found that activation of PPARγ inhibit MEF2D expression via upregulation of miR-122, which can target the 3'-UTR of MEF2D and inhibit MEF2D expression, by directly binding to the PPRE in the miR-122 promoter region...
June 3, 2016: Biochemical and Biophysical Research Communications
Yushi Wang, Jiwen Wang, Hehe Liu, Rongping Zhang, Tao Zhang, Xiang Gan, Huilan Huang, Da Chen, Liang Li
Myocyte enhancer transcription factor 2D (MEF2D) is an important transcription factor for promoting the growth and development of muscle. CAG repeats have been found in the coding sequence (CDS) of avian MEF2D; however, their functions remain unknown and require further investigation. Here, we examined the characteristics and functional role of MEF2D CAG repeat in duck. The full-length CDS of duck MEF2D was cloned for the first time, and a novel CAG repeat was identified and located in exon 9. Sequence analysis indicated that the protein domains of duck MEF2D are highly conserved relative to other vertebrates, whereas MEF2D CAG repeats with variable repeat numbers are specific to avian species...
August 2016: DNA and Cell Biology
Song Guo, Anne Luise Haulund Vollesen, Rikke Dyhr Hansen, Ann-Louise Esserlind, Faisal Mohammed Amin, Anne Francke Christensen, Jes Olesen, Messoud Ashina
BACKGROUND: Intravenous infusion of adenylate cyclase-activating polypeptide-38 (PACAP38) provokes migraine-like attacks in 65-70% of migraine sufferers. Whether aggregation of migraine in first-degree relatives contributes to this discrepancy in PACAP38-induced response is unknown. We hypothesized that genetic enrichment plays a role in triggering of migraine and that migraine without aura patients with a high family load ( ≥ 2 first-degree relatives with migraine) would report more migraine-like attacks after intravenous infusion of human PACAP38...
March 18, 2016: Cephalalgia: An International Journal of Headache
Song Guo, Anne Luise Haulund Vollesen, Young Bae Lee Hansen, Erik Frandsen, Malene Rohr Andersen, Faisal Mohammad Amin, Jan Fahrenkrug, Jes Olesen, Messoud Ashina
BACKGROUND: Intravenous infusion of pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) provokes migraine attacks in 65-70% of migraine without aura (MO) patients. We investigated whether PACAP38 infusion causes changes in the endogenous production of PACAP38, vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), tumour necrosis factor alpha (TNFα), S100 calcium binding protein B (S100B), neuron-specific enolase and pituitary hormones in migraine patients...
March 18, 2016: Cephalalgia: An International Journal of Headache
Bhawna Rastogi, Satish K Raut, Naresh K Panda, Vidya Rattan, Bishan D Radotra, Madhu Khullar
Histone deacetylases (HDACs) are a family of deacetylase enzymes that regulate the acetylation state of histones and a variety of other non-histone proteins including key oncogenic and tumor suppressor proteins, which modulates chromatin conformation, leading to regulation of gene expression. HDACs has been grouped into classes I-IV and histone deacetylase 9 (HDAC9) belongs to class IIa which exhibits tissue-specific expression. Recent reports have demonstrated both pro-oncogenic and tumor suppressive role for HDAC9 in different cancers; however, its role in OSCC remains elusive...
April 2016: Molecular and Cellular Biochemistry
Zi-Wei Chen, Anmin Liu, Qingyu Liu, Jingkao Chen, Wen-Ming Li, Xiao-Juan Chao, Qian Yang, Pei-Qing Liu, Zi-Xu Mao, Rong-Biao Pi
Methylene blue (MB) can ameliorate behavioral, neurochemical, and neuropathological impairments in animal models of acute and chronic neurodegenerative disorders, but the underlying mechanism remains unclear. Myocyte enhancer factor 2 (MEF2D) is known to promote neuronal survival in several models, and several survival and death signals converge on MEF2D and regulate its activity. Here, we investigated the role of MEF2D in the neuroprotective effect of MB against glutamate-induced toxicity in HT22 neuronal cells...
March 3, 2016: Molecular Neurobiology
Alessandro Arosio, Gessica Sala, Virginia Rodriguez-Menendez, Denise Grana, Francesca Gerardi, Christian Lunetta, Carlo Ferrarese, Lucio Tremolizzo
Amyotrophic lateral sclerosis (ALS) is a progressive neuro-muscular disease characterized by motor neuron loss. MEF2D and MEF2C are members of the myocyte enhancer factor 2 family (MEF2), a group of transcription factors playing crucial roles both in muscle and in neural development and maintenance; for this reason, a possible involvement of MEF2 in ALS context has been investigated. Since the transcriptional activity of each tissue specific MEF2 isoform is conserved in different cell types, we chose to assess our parameters in an easily accessible and widely used experimental tool such as peripheral blood mononuclear cells (PBMCs) obtained from 30 sporadic ALS patients (sALS), 9 ALS patients with mutations in SOD1 gene (SOD1+) and 30 healthy controls...
July 2016: Molecular and Cellular Neurosciences
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