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SKA2

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https://www.readbyqxmd.com/read/27822318/discovery-and-replication-of-a-peripheral-tissue-dna-methylation-biosignature-to-augment-a-suicide-prediction-model
#1
Makena L Clive, Marco P Boks, Christiaan H Vinkers, Lauren M Osborne, Jennifer L Payne, Kerry J Ressler, Alicia K Smith, Holly C Wilcox, Zachary Kaminsky
BACKGROUND: Suicide is the second leading cause of death among adolescents in the USA, and rates are rising. Methods to identify individuals at risk are essential for implementing prevention strategies, and the development of a biomarker can potentially improve prediction of suicidal behaviors. Prediction of our previously reported SKA2 biomarker for suicide and PTSD is substantially improved by questionnaires assessing perceived stress or anxiety and is therefore reliant on psychological assessment...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27380775/global-identification-of-hnrnp-a1-binding-sites-for-sso-based-splicing-modulation
#2
Gitte H Bruun, Thomas K Doktor, Jonas Borch-Jensen, Akio Masuda, Adrian R Krainer, Kinji Ohno, Brage S Andresen
BACKGROUND: Many pathogenic genetic variants have been shown to disrupt mRNA splicing. Besides splice mutations in the well-conserved splice sites, mutations in splicing regulatory elements (SREs) may deregulate splicing and cause disease. A promising therapeutic approach is to compensate for this deregulation by blocking other SREs with splice-switching oligonucleotides (SSOs). However, the location and sequence of most SREs are not well known. RESULTS: Here, we used individual-nucleotide resolution crosslinking immunoprecipitation (iCLIP) to establish an in vivo binding map for the key splicing regulatory factor hnRNP A1 and to generate an hnRNP A1 consensus binding motif...
2016: BMC Biology
https://www.readbyqxmd.com/read/27256967/mulibrey-nanism-two-novel-mutations-in-a-child-identified-by-array-cgh-and-dna-sequencing
#3
Enza Mozzillo, Carla Cozzolino, Rita Genesio, Daniela Melis, Giulia Frisso, Ada Orrico, Barbara Lombardo, Valentina Fattorusso, Valentina Discepolo, Roberto Della Casa, Francesca Simonelli, Lucio Nitsch, Francesco Salvatore, Adriana Franzese
In childhood, several rare genetic diseases have overlapping symptoms and signs, including those regarding growth alterations, thus the differential diagnosis is sometimes difficult. The proband, aged 3 years, was suspected to have Silver-Russel syndrome because of intrauterine growth retardation, postnatal growth retardation, typical facial dysmorphic features, macrocephaly, body asymmetry, and bilateral fifth finger clinodactyly. Other features were left atrial and ventricular enlargement and patent foramen ovale...
August 2016: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/27121316/epigenetic-modification-of-mir-141-regulates-ska2-by-an-endogenous-sponge-hotair-in-glioma
#4
Er-Bao Bian, Chun-Chun Ma, Xiao-Jun He, Chao Wang, Gang Zong, Hong-Liang Wang, Bing Zhao
Aberrant expression of miR-141 has recently implicated in the occurrence and development of various types of malignant tumors. However whether the involvement of miR-141 in the pathogenesis of glioma remains unknown. Here, we showed that miR-141 was markedly downregulated in glioma tissues and cell lines compared with normal brain tissues, and its expression correlated with the pathological grading. Enforced expression of miR-141 in glioma cells significantly inhibited cell proliferation, migration and invasion, whereas knockdown of miR-141 exerted opposite effect...
May 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27038412/epigenetic-variation-at-ska2-predicts-suicide-phenotypes-and-internalizing-psychopathology
#5
Naomi Sadeh, Erika J Wolf, Mark W Logue, Jasmeet P Hayes, Annjanette Stone, L Michelle Griffin, Steven A Schichman, Mark W Miller
BACKGROUND: DNA methylation of the SKA2 gene has recently been implicated as a biomarker of suicide risk and posttraumatic stress disorder (PTSD). To examine the specificity and reliability of these findings, we examined associations between SKA2 DNA methylation, broad dimensions of psychiatric symptoms, and suicide phenotypes in adults with high levels of trauma exposure. METHODS: A total of 466 White, non-Hispanic veterans and their intimate partners (65% male) underwent clinical assessment and had blood drawn for genotyping and methylation analysis...
April 2016: Depression and Anxiety
https://www.readbyqxmd.com/read/27030168/glucocorticoid-receptor-related-genes-genotype-and-brain-gene-expression-relationships-to-suicide-and-major-depressive-disorder
#6
Honglei Yin, Hanga Galfalvy, Spiro P Pantazatos, Yung-Yu Huang, Gorazd B Rosoklija, Andrew J Dwork, Ainsley Burke, Victoria Arango, Maria A Oquendo, J John Mann
INTRODUCTION: We tested the relationship between genotype, gene expression and suicidal behavior and major depressive disorder (MDD) in live subjects and postmortem samples for three genes, associated with the hypothalamic-pituitary-adrenal axis, suicidal behavior, and MDD; FK506-binding protein 5 (FKBP5), Spindle and kinetochore-associated protein 2 (SKA2), and Glucocorticoid Receptor (NR3C1). MATERIALS AND METHODS: Single-nucleotide polymorphisms (SNPs) and haplotypes were tested for association with suicidal behavior and MDD in a live (N = 277) and a postmortem sample (N = 209)...
June 2016: Depression and Anxiety
https://www.readbyqxmd.com/read/26902949/the-expression-of-the-suicide-associated-gene-ska2-is-decreased-in-the-prefrontal-cortex-of-suicide-victims-but-not-of-nonsuicidal-patients
#7
Ghanshyam N Pandey, Hooriyah S Rizavi, Hui Zhang, Runa Bhaumik, Xinguo Ren
BACKGROUND: Recent study of genome-wide DNA methylation profiling in the postmortem brain of suicidal and nonsuicidal subjects found that gene expression of spindle and kinetochore associated complex subunit 2 (SKA2) is decreased in the postmortem brain of suicide victims compared with nonsuicidal, nonpsychiatric control subjects. METHODS: To determine if decreased SKA2 is specific to suicide and independent of diagnosis, we determined gene and protein expression of SKA2 in the prefrontal cortex obtained from suicide victims (n= 52), nonsuicidal psychiatric subjects (n= 27), and normal controls (n= 24)...
August 2016: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/26887336/ska2-methylation-predicts-reduced-cortical-thickness-in-prefrontal-cortex
#8
N Sadeh, J M Spielberg, M W Logue, E J Wolf, A K Smith, J Lusk, J P Hayes, E Sperbeck, W P Milberg, R E McGlinchey, D H Salat, W C Carter, A Stone, S A Schichman, D E Humphries, M W Miller
No abstract text is available yet for this article.
March 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/26824422/cyclic-amp-responsive-element-binding-protein-promotes-renal-cell-carcinoma-proliferation-probably-via-the-expression-of-spindle-and-kinetochore-associated-protein-2
#9
Haihui Zhuang, Xiangyu Meng, Yanyuan Li, Xue Wang, Shuaishuai Huang, Kaitai Liu, Michael Hehir, Rong Fang, Lei Jiang, Jeff X Zhou, Ping Wang, Yu Ren
Emerging evidence shows that the aberrantly expressed cyclic AMP responsive element-binding protein (CREB) is associated with tumor development and progression in several cancers. Spindle and kinetochore-associated protein 2 (SKA2) is essential for regulating the progress of mitosis. In this study, we evaluate in vitro and in vivo the functional relationship between CREB and SKA2 in renal cell carcinoma (RCC). Suppressing and replenishing CREB levels were used to manipulate SKA2 expression, observing the effects on RCC cell lines...
March 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/26460070/peroxisome-proliferator-activated-receptor-%C3%AE-mediated-transcription-of-mir-301a-and-mir-454-and-their-host-gene-ska2-regulates-endothelin-1-and-pai-1-expression-in-sickle-cell-disease
#10
Caryn S Gonsalves, Chen Li, Punam Malik, Stanley M Tahara, Vijay K Kalra
Endothelin-1 (ET-1) and plasminogen activator inhibitor-1 (PAI-1) play important roles in pulmonary hypertension (PH) in sickle cell disease (SCD). Our previous studies show higher levels of placenta growth factor (PlGF) in SCD correlate with increased plasma levels of ET-1, PAI-1, and other physiological markers of PH. PlGF-mediated ET-1 and PAI-1 expression occurs via activation of hypoxia-inducible factor-1α (HIF-1α). However, relatively little is understood regarding post-transcriptional regulation of PlGF-mediated expression of ET-1 and PAI-1...
October 12, 2015: Bioscience Reports
https://www.readbyqxmd.com/read/26361058/ska2-methylation-is-involved-in-cortisol-stress-reactivity-and-predicts-the-development-of-post-traumatic-stress-disorder-ptsd-after-military-deployment
#11
Marco P Boks, Bart P F Rutten, Elbert Geuze, Lotte C Houtepen, Eric Vermetten, Zachary Kaminsky, Christiaan H Vinkers
Genomic variation in the SKA2 gene has recently been identified as a promising suicide biomarker. In light of its role in glucocorticoid receptor transactivation, we investigated whether SKA2 DNA methylation influences cortisol stress reactivity and is involved in the development of post-traumatic stress disorder (PTSD). Increased SKA2 methylation was significantly associated with lower cortisol stress reactivity in 85 healthy individuals exposed to the Trier Social Stress Test (B=-173.40, t=-2.324, p-value=0...
April 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/26324104/ska2-methylation-is-associated-with-decreased-prefrontal-cortical-thickness-and-greater-ptsd-severity-among-trauma-exposed-veterans
#12
N Sadeh, J M Spielberg, M W Logue, E J Wolf, A K Smith, J Lusk, J P Hayes, E Sperbeck, W P Milberg, R E McGlinchey, D H Salat, W C Carter, A Stone, S A Schichman, D E Humphries, M W Miller
Methylation of the SKA2 (spindle and kinetochore-associated complex subunit 2) gene has recently been identified as a promising biomarker of suicide risk. Based on this finding, we examined associations between SKA2 methylation, cortical thickness and psychiatric phenotypes linked to suicide in trauma-exposed veterans. About 200 trauma-exposed white non-Hispanic veterans of the recent conflicts in Iraq and Afghanistan (91% male) underwent clinical assessment and had blood drawn for genotyping and methylation analysis...
March 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/26305478/epigenetic-and-genetic-variation-at-ska2-predict-suicidal-behavior-and-post-traumatic-stress-disorder
#13
Z Kaminsky, H C Wilcox, W W Eaton, K Van Eck, V Kilaru, T Jovanovic, T Klengel, B Bradley, E B Binder, K J Ressler, A K Smith
Traumatic stress results in hypothalamic pituitary adrenal (HPA) axis abnormalities and an increased risk to both suicidal behaviors and post-traumatic stress disorder (PTSD). Previous work out of our laboratory identified SKA2 DNA methylation associations with suicidal behavior in the blood and brain of multiple cohorts. Interaction of SKA2 with stress predicted suicidal behavior with ~80% accuracy. SKA2 is hypothesized to reduce the ability to suppress cortisol following stress, which is of potentially high relevance in traumatized populations...
2015: Translational Psychiatry
https://www.readbyqxmd.com/read/26283638/understanding-and-predicting-suicidality-using-a-combined-genomic-and-clinical-risk-assessment-approach
#14
A B Niculescu, D F Levey, P L Phalen, H Le-Niculescu, H D Dainton, N Jain, E Belanger, A James, S George, H Weber, D L Graham, R Schweitzer, T B Ladd, R Learman, E M Niculescu, N P Vanipenta, F N Khan, J Mullen, G Shankar, S Cook, C Humbert, A Ballew, M Yard, T Gelbart, A Shekhar, N J Schork, S M Kurian, G E Sandusky, D R Salomon
Worldwide, one person dies every 40 seconds by suicide, a potentially preventable tragedy. A limiting step in our ability to intervene is the lack of objective, reliable predictors. We have previously provided proof of principle for the use of blood gene expression biomarkers to predict future hospitalizations due to suicidality, in male bipolar disorder participants. We now generalize the discovery, prioritization, validation, and testing of such markers across major psychiatric disorders (bipolar disorder, major depressive disorder, schizoaffective disorder, and schizophrenia) in male participants, to understand commonalities and differences...
November 2015: Molecular Psychiatry
https://www.readbyqxmd.com/read/26224029/anemone-altaica-induces-apoptosis-in-human-osteosarcoma-cells
#15
I-Chang Chang, Tsay-I Chiang, Chun Lo, Yi-Hua Lai, Chia-Herng Yue, Jer-Yuh Liu, Li-Sung Hsu, Chia-Jen Lee
In the past decade, no significant improvement has been made in chemotherapy for osteosarcoma (OS). To develop improved agents against OS, we screened 70 species of medicinal plants and treated two human OS cell lines with different agent concentrations. We then examined cell viability using the MTT assay. Results showed that a candidate plant, particularly the rhizomes of Anemone altaica Fisch. ex C. A. Mey aqueous extract (AAE), suppressed the viability of HOS and U2OS cells in a concentration-dependent manner...
2015: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/26162986/the-gene-pair-prr11-and-ska2-shares-a-nf-y-regulated-bidirectional-promoter-and-contributes-to-lung-cancer-development
#16
Yitao Wang, Ying Zhang, Chundong Zhang, Huali Weng, Yi Li, Wei Cai, Mengyu Xie, Yinjiang Long, Qing Ai, Zhu Liu, Gang Du, Sen Wang, Yulong Niu, Fangzhou Song, Toshinori Ozaki, Youquan Bu
Head-to-head gene pairs represent a unique feature of gene organization in eukaryotes, accounting for >10% of genes in the human genome. Identification and functional analysis of such gene pairs is only in its infancy. Recently, we identified PRR11 as a novel cancer-related gene that is implicated in cell cycle and lung cancer. Here we demonstrate that PRR11 is oriented in a head-to-head configuration with its neighboring gene, SKA2. 5'-RACE assay revealed that the intergenic spacer region between the two genes is <500 bp...
September 2015: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/25582618/psychiatric-blood-biomarkers-avoiding-jumping-to-premature-negative-or-positive-conclusions
#17
A B Niculescu, D Levey, H Le-Niculescu, E Niculescu, S M Kurian, D Salomon
Blood biomarkers may provide a scientifically useful and clinically usable peripheral signal in psychiatry, as they have been doing for other fields of medicine. Jumping to premature conclusions, negative or positive, can create confusion in this field. Reproducibility is a hallmark of good science. We discuss some recent examples from this dynamic field, and show some new data in support of previously published biomarkers for suicidality (SAT1, MARCKS and SKA2). Methodological clarity and rigor in terms of biomarker discovery, validation and testing is needed...
March 2015: Molecular Psychiatry
https://www.readbyqxmd.com/read/25073599/identification-and-replication-of-a-combined-epigenetic-and-genetic-biomarker-predicting-suicide-and-suicidal-behaviors
#18
Jerry Guintivano, Tori Brown, Alison Newcomer, Marcus Jones, Olivia Cox, Brion S Maher, William W Eaton, Jennifer L Payne, Holly C Wilcox, Zachary A Kaminsky
Considerable research suggests that suicide involves effects of genes, the environment, and their interaction. Analysis of three independent data sets of post-mortem brains revealed signs of increased methylation in one particular gene, SKA2, a finding that was extended to peripheral blood samples from other cohorts of prospectively followed individuals.
December 1, 2014: American Journal of Psychiatry
https://www.readbyqxmd.com/read/24871663/novel-target-genes-responsive-to-apoptotic-activity-by-ocimum-gratissimum-in-human-osteosarcoma-cells
#19
Chien-Chung Lin, Pei-Yu Chao, Chia-Yao Shen, Jyuan-Jen Shu, Shiow-Kang Yen, Chih-Yang Huang, Jer-Yuh Liu
Osteosarcoma (OS) is a type of bone cancer. Eighty percent of this tumor will metastasize to the lungs or liver, and as a result, patients generally need chemotherapy to improve survival possibility. Recently, antitumor activity has been reported in Ocimum gratissimum aqueous extract (OGE), which has been the focus of recent extensive studies on therapeutic strategies due to its antioxidant properties. We performed pharmacogenomics analyses for the effect of OGE on human osteosarcoma U2-OS and HOS cell growth...
2014: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/23765286/resonance-assignments-of-the-microtubule-binding-domain-of-the-c-elegans-spindle-and-kinetochore-associated-protein-1
#20
Andras Boeszoermenyi, Jens C Schmidt, Iain M Cheeseman, Monika Oberer, Gerhard Wagner, Haribabu Arthanari
During mitosis, kinetochores coordinate the attachment of centromeric DNA to the dynamic plus ends of microtubules, which is hypothesized to pull sister chromatids toward opposing poles of the mitotic spindle. The outer kinetochore Ndc80 complex acts synergistically with the Ska (spindle and kinetochore-associated) complex to harness the energy of depolymerizing microtubules and power chromosome movement. The Ska complex is a hexamer consisting of two copies of the proteins Ska1, Ska2 and Ska3, respectively...
October 2014: Biomolecular NMR Assignments
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