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https://www.readbyqxmd.com/read/28511095/independent-validation-of-dna-based-approaches-for-age-prediction-in-blood
#1
Sohee Cho, Sang-Eun Jung, Sae Rom Hong, Eun Hee Lee, Ji Hyun Lee, Soong Deok Lee, Hwan Young Lee
Numerous molecular biomarkers have been proposed as predictors of chronological age. Among them, T-cell specific DNA rearrangement and DNA methylation markers have been introduced as forensic age predictors in blood because of their high prediction accuracy. These markers appear highly promising, but for better application to forensic casework sample analysis the proposed markers and genotyping methods must be tested further. In the current study, signal-joint T-cell receptor excision circles (sjTRECs) and DNA methylation markers located in the ELOVL2, C1orf132, TRIM59, KLF14, and FHL2 genes were reanalyzed in 100 Korean blood samples to test their associations with chronological age, using the same analysis platform used in previous reports...
April 28, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/28499412/genome-wide-dna-methylation-analysis-reveals-hypomethylation-in-the-low-cpg-promoter-regions-in-lymphoblastoid-cell-lines
#2
Itsuki Taniguchi, Chihiro Iwaya, Keizo Ohnaka, Hiroki Shibata, Ken Yamamoto
BACKGROUND: Epidemiological studies of DNA methylation profiles may uncover the molecular mechanisms through which genetic and environmental factors contribute to the risk of multifactorial diseases. There are two types of commonly used DNA bioresources, peripheral blood cells (PBCs) and EBV-transformed lymphoblastoid cell lines (LCLs), which are available for genetic epidemiological studies. Therefore, to extend our knowledge of the difference in DNA methylation status between LCLs and PBCs is important in human population studies that use these DNA sources to elucidate the epigenetic risks for multifactorial diseases...
May 12, 2017: Human Genomics
https://www.readbyqxmd.com/read/28489964/specific-activation-of-plekhg2-induced-serum-response-element-dependent-gene-transcription-by-four-and-a-half-lim-domains-fhl-1-but-not-fhl2-or-fhl3
#3
Masashi Nishikawa, Katsuya Sato, Shun Nakano, Hisashi Yamakawa, Takahiro Nagase, Hiroshi Ueda
PLEKHG2 is a Gβγ- and Gαs-dependent guanine nucleotide exchange factor for Rac1 and Cdc42 small GTPases and has been shown to mediate signaling pathways such as those for actin cytoskeletal reorganization and serum response element (SRE)-dependent gene transcription. We have shown that the four-and-a-half LIM domains (FHL) 1 acts as a positive regulator of PLEKHG2. Here, we evaluated the other FHL family members and found that the FHL1A specifically regulate the PLEKHG2 activity. Moreover, FHL1A further enhanced Gβγ- and PLEKHG2-induced SRE-dependent gene transcription, whereas FHL1A partially restored the attenuated PLEKHG2-induced SRE-dependent gene transcription by Gαs...
May 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28423572/acceleration-of-leukocytes-epigenetic-age-as-an-early-tumor-and-sex-specific-marker-of-breast-and-colorectal-cancer
#4
Danielle Fernandes Durso, Maria Giulia Bacalini, Claudia Sala, Chiara Pirazzini, Elena Marasco, Massimiliano Bonafé, Ítalo Faria do Valle, Davide Gentilini, Gastone Castellani, Ana Maria Caetano Faria, Claudio Franceschi, Paolo Garagnani, Christine Nardini
Changes in blood epigenetic age have been associated with several pathological conditions and have recently been described to anticipate cancer development. In this work, we analyze a publicly available leukocytes methylation dataset to evaluate the relation between DNA methylation age and the prospective development of specific types of cancer. We calculated DNA methylation age acceleration using five state-of-the-art estimators (three multi-site: Horvath, Hannum, Weidner; and two CpG specific: ELOV2 and FHL2) in a cohort including 845 subjects from the EPIC-Italy project and we compared 424 samples that remained cancer-free over the approximately ten years of follow-up with 235 and 166 subjects who developed breast and colorectal cancer, respectively...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402264/fhl2-interacts-with-iaspp-and-impacts-the-biological-functions-of-leukemia-cells
#5
Wenting Lu, Tengteng Yu, Shuang Liu, Saisai Li, Shouyun Li, Jia Liu, Yingxi Xu, Haiyan Xing, Zheng Tian, Kejing Tang, Qing Rao, Jianxiang Wang, Min Wang
iASPP is an inhibitory member of apoptosis-stimulating proteins of p53 (ASPP) family, which inhibits p53-dependent apoptosis. iASPP was highly expressed in acute leukemia, inhibited leukemia cells apoptosis and promoted leukemogenesis. In order to clarify its mechanism, a yeast two-hybrid screen was performed and FHL2 was identified for the first time as one of the binding proteins of iASPP. FHL2 was highly expressed in K562 and Kasumi-1 cells. FHL2 and iASPP interacted with each other and co-localized in both nucleus and cytoplasm...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28349819/adam-17-fhl2-colocalisation-suggests-interaction-and-role-of-these-proteins-in-colorectal-cancer
#6
Laurine Verset, Joke Tommelein, Christine Decaestecker, Elly De Vlieghere, Marc Bracke, Isabelle Salmon, Olivier De Wever, Pieter Demetter
FHL2 is a multifunctional scaffolding protein; its expression is associated with poor prognosis in colorectal cancer. ADAM-17 is a metalloprotease implicated in ectodomain shedding. FHL2 regulates ADAM-17 plasma membrane localisation, and FHL2 deficiency leads to decreased activity of ADAM-17 in mouse macrophages. Presence and relationship of the ADAM-17/FHL2 complex with colorectal cancer progression is unknown. We studied FHL2 and ADAM-17 expression in several colon cancer cell lines by immunocytochemistry and western blot...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28320530/single-cell-rna-sequence-analysis-of-mouse-glomerular-mesangial-cells-uncovers-mesangial-cell-essential-genes
#7
Yuqiu Lu, Yuting Ye, Qianqian Yang, Shaolin Shi
Mesangial cells are essential for the structure and function of glomeruli, but the mechanisms underlying these roles are not well understood. Here, we performed a single-cell RNA-sequence (RNA-seq) analysis of mouse mesangial cells using the Fluidigm C1 platform. We found that gene expression in individual mesangial cells was tremendously heterogeneous, with mean correlation coefficients of 0.20, and most mesangial genes were actually expressed in only a portion of mesangial cells and are therefore presumably dispensable...
March 17, 2017: Kidney International
https://www.readbyqxmd.com/read/28243234/fhl2-regulates-natural-killer-cell-development-and-activation-during-streptococcus-pneumoniae-infection
#8
Thomas Baranek, Eric Morello, Alexandre Valayer, Rose-France Aimar, Déborah Bréa, Clemence Henry, Anne-Gaelle Besnard, Emilie Dalloneau, Antoine Guillon, Pierre-François Dequin, Emilie Narni-Mancinelli, Eric Vivier, Fabrice Laurent, Yu Wei, Christophe Paget, Mustapha Si-Tahar
Recent in silico studies suggested that the transcription cofactor LIM-only protein FHL2 is a major transcriptional regulator of mouse natural killer (NK) cells. However, the expression and role of FHL2 in NK cell biology are unknown. Here, we confirm that FHL2 is expressed in both mouse and human NK cells. Using FHL2(-/-) mice, we found that FHL2 controls NK cell development in the bone marrow and maturation in peripheral organs. To evaluate the importance of FHL2 in NK cell activation, FHL2(-/-) mice were infected with Streptococcus pneumoniae...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28223370/the-lim-only-protein-fhl2-is-a-negative-regulator-of-tgf-%C3%AE-1-expression
#9
Jennifer Dahan, Florence Levillayer, Tian Xia, Yann Nouët, Catherine Werts, Martine Fanton d'Andon, Minou Adib-Conquy, Anne-Marie Cassard-Doulcier, Varun Khanna, Ju Chen, Thierry Tordjmann, Marie-Annick Buendia, Grégory Jouvion, Yu Wei
TGF-β1 is a master cytokine in many biological processes including tissue homeostasis, epithelial to mesenchymal transition and wound repair. Here we report that the four and a half LIM-only protein 2 (FHL2) is a critical regulator of TGF-β1 expression. Devoid of DNA-binding domain, FHL2 is a transcriptional co-factor that plays the role of co-activator or co-repressor depending on the cell and promoter contexts. We detected association of FHL2 with the TGF-β1 promoter, which showed higher activity in Fhl2(-/-) cells than WT cells in a reporter assay...
February 21, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27892920/foxk1-interaction-with-fhl2-promotes-proliferation-invasion-and-metastasis-in-colorectal-cancer
#10
M Wu, J Wang, W Tang, X Zhan, Y Li, Y Peng, X Huang, Y Bai, J Zhao, A Li, C Chen, Y Chen, H Peng, Y Ren, G Li, S Liu, J Wang
The transcriptional factor Forkhead box k1 (FOXK1) is a member of the FOX family. The abnormal expression of FOXK1 may have an important role in tumour development. Our previous studies showed that four-and-a-half LIM protein 2 (FHL2) is a critical inducer of the epithelial-to-mesenchymal transition (EMT) and invasion. However, the molecular mechanism by which FOXK1 synergizes with FHL2 tumour proliferation, EMT and metastasis is not well defined. We evaluated that messenger RNA (mRNA) and protein expression levels by quantitative RT-PCR, western blot, immunofluorescence and immunohistochemistry (IHC) assays...
November 28, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27742790/matrix-mechanics-controls-fhl2-movement-to-the-nucleus-to-activate-p21-expression
#11
Naotaka Nakazawa, Aneesh R Sathe, G V Shivashankar, Michael P Sheetz
Substrate rigidity affects many physiological processes through mechanochemical signals from focal adhesion (FA) complexes that subsequently modulate gene expression. We find that shuttling of the LIM domain (domain discovered in the proteins, Lin11, Isl-1, and Mec-3) protein four-and-a-half LIM domains 2 (FHL2) between FAs and the nucleus depends on matrix mechanics. In particular, on soft surfaces or after the loss of force, FHL2 moves from FAs into the nucleus and concentrates at RNA polymerase (Pol) II sites, where it acts as a transcriptional cofactor, causing an increase in p21 gene expression that will inhibit growth on soft surfaces...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27672102/systemic-age-associated-dna-hypermethylation-of-elovl2-gene-in-vivo-and-in-vitro-evidences-of-a-cell-replication-process
#12
Maria Giulia Bacalini, Joris Deelen, Chiara Pirazzini, Marco De Cecco, Cristina Giuliani, Catia Lanzarini, Francesco Ravaioli, Elena Marasco, Diana van Heemst, H Eka D Suchiman, Roderick Slieker, Enrico Giampieri, Rina Recchioni, Fiorella Mercheselli, Stefano Salvioli, Giovanni Vitale, Fabiola Olivieri, Annemieke M W Spijkerman, Martijn E T Dollé, John M Sedivy, Gastone Castellani, Claudio Franceschi, Pieternella E Slagboom, Paolo Garagnani
Epigenetic remodeling is one of the major features of the aging process. We recently demonstrated that DNA methylation of ELOVL2 and FHL2 CpG islands is highly correlated with age in whole blood. Here we investigated several aspects of age-associated hypermethylation of ELOVL2 and FHL2 We showed that ELOVL2 methylation is significantly different in primary dermal fibroblast cultures from donors of different ages. Using epigenomic data from public resources, we demonstrated that most of the tissues show ELOVL2 and FHL2 hypermethylation with age...
September 26, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/27622035/missense-mutations-in-the-perforin-prf1-gene-as-a-cause-of-hereditary-cancer-predisposition
#13
Mohammed S Chaudhry, Kimberly C Gilmour, Imran G House, Mark Layton, Nicki Panoskaltsis, Mamta Sohal, Joseph A Trapani, Ilia Voskoboinik
Perforin, a pore-forming toxin released from secretory granules of NK cells and CTLs, is essential for their cytotoxic activity against infected or cancerous target cells. Bi-allelic loss-of-function mutations in the perforin gene are invariably associated with a fatal immunoregulatory disorder, familial haemophagocytic lymphohistiocytosis type 2 (FHL2), in infants. More recently, it has also been recognized that partial loss of perforin function can cause disease in later life, including delayed onset FHL2 and haematological malignancies...
July 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27602173/donor-age-and-c1orf132-mir29b2c-determine-age-related-methylation-signature-of-blood-after-allogeneic-hematopoietic-stem-cell-transplantation
#14
LETTER
Magdalena Spólnicka, Renata Zbieć Piekarska, Emilia Jaskuła, Grzegorz W Basak, Renata Jacewicz, Agnieszka Pięta, Żanetta Makowska, Maciej Jedrzejczyk, Agnieszka Wierzbowska, Agnieszka Pluta, Tadeusz Robak, Jarosław Berent, Wojciech Branicki, Wiesław Jędrzejczak, Andrzej Lange, Rafał Płoski
BACKGROUND: Our recent study demonstrated that DNA methylation status in a set of CpGs located in ELOVL2, C1orf132, TRIM59, KLF14, and FHL2 can accurately predict calendar age in blood. In the present work, we used these markers to evaluate the effect of allogeneic hematopoietic stem cell transplantation (HSCT) on the age-related methylation signature of human blood. METHODS: DNA methylation in 32 CpGs was investigated in 16 donor-recipient pairs using pyrosequencing...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27497326/forensic-age-prediction-for-dead-or-living-samples-by-use-of-methylation-sensitive-high-resolution-melting
#15
Yuya Hamano, Sho Manabe, Chie Morimoto, Shuntaro Fujimoto, Munetaka Ozeki, Keiji Tamaki
Age prediction with epigenetic information is now edging closer to practical use in forensic community. Many age-related CpG (AR-CpG) sites have proven useful in predicting age in pyrosequencing or DNA chip analyses. In this study, a wide range methylation status in the ELOVL2 and FHL2 promoter regions were detected with methylation-sensitive high resolution melting (MS-HRM) in a labor-, time-, and cost-effective manner. Non-linear-distributions of methylation status and chronological age were newly fitted to the logistic curve...
July 2016: Legal Medicine
https://www.readbyqxmd.com/read/27452873/identification-of-common-and-differential-mechanisms-of-glomerulus-and-tubule-senescence-in-24-month-old-rats-by-quantitative-lc-ms-ms
#16
Shiyu Wang, Yang Lu, Xuefeng Sun, Di Wu, Bo Fu, Yuling Chen, Haiteng Deng, Xiangmei Chen
Kidney aging together with related renal disease had become a major clinical problem. Understanding the mechanisms of aging was important for suspending senescence and decreasing the incidence of aging-related diseases. In the present work, 24-month-old F344 rats were used as aging rats and 3-month-old rats were used as young controls. Senescence-associated-β-galactosidase staining results showed that the degree of senescence in renal tubules was more severe than that in glomeruli. We performed quantitative LC-MS to assess the differential protein expression profiles of senescent glomeruli and tubules...
October 2016: Proteomics
https://www.readbyqxmd.com/read/27446400/plumbagin-exhibits-an-anti-proliferative-effect-in-human-osteosarcoma-cells-by-downregulating-fhl2-and-interfering-with-wnt-%C3%AE-catenin-signalling
#17
Yuan-Liang Xue, Xiang-Qi Meng, Long-Jun Ma, Zhen Yuan
Plumbagin, a naphthoquinone constituent of Plumbago zeylanica L. (Plumbaginaceae) is widely used in traditional Chinese medicine as an antifungal, antibacterial and anti-inflammatory agent. Plumbagin is known to exhibit proapoptotic, antiangiogenic and antimetastatic effects in cancer cells. The transcriptional co-factor four and a half LIM domains 2 (FHL2) is a multifunctional adaptor protein that is involved in the regulation of gene expression, signal transduction and cell proliferation and differentiation, and also acts as a tumor suppressor or oncoprotein depending on the tissue microenvironment...
August 2016: Oncology Letters
https://www.readbyqxmd.com/read/27415427/the-four-and-a-half-lim-domains-2-fhl2-regulates-ovarian-granulosa-cell-tumor-progression-via-controlling-akt1-transcription
#18
G Hua, C He, X Lv, L Fan, C Wang, S W Remmenga, K J Rodabaugh, L Yang, S M Lele, P Yang, A R Karpf, J S Davis, C Wang
The four and a half LIM domains 2 (FHL2) has been shown to play important roles in the regulation of cell proliferation, survival, adhesion, motility and signal transduction in a cell type and tissue-dependent manner. However, the function of FHL2 in ovarian physiology and pathology is unclear. The aim of this study was to determine the role and functional mechanism of FHL2 in the progression of ovarian granulosa cell tumors (GCTs). Immunohistochemical analysis indicated that FHL2 was overexpressed in GCT tissues...
2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27364902/tissue-microarray-profiling-in-human-heart-failure
#19
Sean Lal, Lisa Nguyen, Rhenan Tezone, Fredrik Ponten, Jacob Odeberg, Amy Li, Cristobal Dos Remedios
Tissue MicroArrays (TMAs) are a versatile tool for high-throughput protein screening, allowing qualitative analysis of a large number of samples on a single slide. We have developed a customizable TMA system that uniquely utilizes cryopreserved human cardiac samples from both heart failure and donor patients to produce formalin-fixed paraffin-embedded sections. Confirmatory upstream or downstream molecular studies can then be performed on the same (biobanked) cryopreserved tissue. In a pilot study, we applied our TMAs to screen for the expression of four-and-a-half LIM-domain 2 (FHL2), a member of the four-and-a-half LIM family...
September 2016: Proteomics
https://www.readbyqxmd.com/read/27337627/development-of-a-methylation-marker-set-for-forensic-age-estimation-using-analysis-of-public-methylation-data-and-the-agena-bioscience-epityper-system
#20
A Freire-Aradas, C Phillips, A Mosquera-Miguel, L Girón-Santamaría, A Gómez-Tato, M Casares de Cal, J Álvarez-Dios, J Ansede-Bermejo, M Torres-Español, P M Schneider, E Pośpiech, W Branicki, Á Carracedo, M V Lareu
Individual age estimation has the potential to provide key information that could enhance and extend DNA intelligence tools. Following predictive tests for externally visible characteristics developed in recent years, prediction of age could guide police investigations and improve the assessment of age-related phenotype expression patterns such as hair colour changes and early onset of male pattern baldness. DNA methylation at CpG positions has emerged as the most promising DNA tests to ascertain the individual age of the donor of a biological contact trace...
September 2016: Forensic Science International. Genetics
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