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https://www.readbyqxmd.com/read/27892920/foxk1-interaction-with-fhl2-promotes-proliferation-invasion-and-metastasis-in-colorectal-cancer
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27271812/predominant-neurological-manifestations-seen-in-a-patient-with-a-biallelic-perforin1-mutation-prf1-p-r225w
#12
Manisha Madkaikar, Maya Gupta, Ashish Dixit, Veerendra Patil
Neurological manifestations in familial hemophagocytic lymphohistiocytosis (FHL) are common, seen in up to 73% of patients in their course of disease. However, in majority of the cases central nervous system manifestations are associated with other clinical and laboratory parameters of hemophagocytic lymphohistiocytosis. We report here a case with FHL2 in whom hemophagocytic lymphohistiocytosis was a presenting manifestation which responded to specific therapy, however, there was isolated central nervous system relapse while patient was in remission and off therapy...
June 6, 2016: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/27176150/nuclear-epicd-expression-and-its-role-in-hepatocellular-carcinoma
#13
Shin Young Park, Jun Sang Bae, Eun Jung Cha, Hyun Hee Chu, Jang Sihn Sohn, Woo Sung Moon
Regulated intramembrane proteolysis of epithelial cell adhesion molecule (EpCAM) results in shedding of the extracellular domain (EpEX) and release of the intra-cellular domain (EpICD) into the cytoplasm. Released EpICD associates with FHL2, β-catenin and Lef-1 to form a nuclear complex and triggers oncogenic signaling. This study was conducted to examine the nuclear expression of EpICD in hepatocellular carcinoma (HCC) and to assess the role of EpICD in HCC. EpICD immunoexpression was examined in 100 cases of HCC using tissue microarrays and correlated with clinicopathological parameters...
July 2016: Oncology Reports
https://www.readbyqxmd.com/read/27129278/mammalian-actin-binding-protein-1-hip-55-interacts-with-fhl2-and-negatively-regulates-cell-invasion
#14
Lindsy R Boateng, David Bennin, Sofia De Oliveira, Anna Huttenlocher
Mammalian actin-binding protein-1 (mAbp1) is an adaptor protein that binds actin and modulates scission during endocytosis. Recent studies suggest that mAbp1 impairs cell invasion; however, the mechanism for the inhibitory effects of mAbp1 remain unclear. We performed a yeast two-hybrid screen and identified the adaptor protein, FHL2, as a novel binding partner that interacts with the N-terminal actin depolymerizing factor homology domain (ADFH) domain of mAbp1. Here we report that depletion of mAbp1 or ectopic expression of the ADFH domain of mAbp1 increased Rho GTPase signaling and breast cancer cell invasion...
July 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27033761/-expression-of-porforin-and-granzyme-b-in-familial-hemophagocytic-lymphohistiocytosis
#15
X H Zhou, J M Luo, Q Bin, X H Huang
OBJECTIVE: To analyze the correlation between genetic variants of PRF1 and expression level of perforin and granzyme B protein, and further determine the relationship between PRF1 gene variants and cytotoxic T lymphocyte/natural killer (CTL/NK) cell function in famililal hemophagocytic lymphohistiocytosis (FHL2). METHODS: Eight children of FHL2 (P1-P8) after treatment, as well as parents and siblings of P1-P5 were included, and thirty healthy children came for physical examination were designated as controls...
March 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/27029739/blood-based-biomarkers-of-age-associated-epigenetic-changes-in-human-islets-associate-with-insulin-secretion-and-diabetes
#16
Karl Bacos, Linn Gillberg, Petr Volkov, Anders H Olsson, Torben Hansen, Oluf Pedersen, Anette Prior Gjesing, Hans Eiberg, Tiinamaija Tuomi, Peter Almgren, Leif Groop, Lena Eliasson, Allan Vaag, Tasnim Dayeh, Charlotte Ling
Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26-74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes identified in human islets (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin secretion and T2D...
March 31, 2016: Nature Communications
https://www.readbyqxmd.com/read/26973248/scaffold-protein-fhl2-facilitates-mdm2-mediated-degradation-of-ier3-to-regulate-proliferation-of-cervical-cancer-cells
#17
H Jin, K Lee, Y-H Kim, H K Oh, Y-I Maeng, T-H Kim, D-S Suh, J Bae
The expression of immediate early response 3 (IER3), a protein with a short half-life, is rapidly induced by various cellular stimuli. We recently reported that IER3 induces the apoptosis of cervical cancer cells and that its expression is downregulated in patients with cervical cancer. However, the molecular mechanism involved in the rapid degradation of IER3 remains unknown. Here, we demonstrate that MDM2 is an E3 ligase that interacts with IER3 and promotes its ubiquitination, followed by proteasomal degradation...
September 29, 2016: Oncogene
https://www.readbyqxmd.com/read/26938915/combined-use-of-gene-expression-modeling-and-sirna-screening-identifies-genes-and-pathways-which-enhance-the-activity-of-cisplatin-when-added-at-no-effect-levels-to-non-small-cell-lung-cancer-cells-in-vitro
#18
Ada W Y Leung, Stacy S Hung, Ian Backstrom, Daniel Ricaurte, Brian Kwok, Steven Poon, Steven McKinney, Romulo Segovia, Jenna Rawji, Mohammed A Qadir, Samuel Aparicio, Peter C Stirling, Christian Steidl, Marcel B Bally
Platinum-based combination chemotherapy is the standard treatment for advanced non-small cell lung cancer (NSCLC). While cisplatin is effective, its use is not curative and resistance often emerges. As a consequence of microenvironmental heterogeneity, many tumour cells are exposed to sub-lethal doses of cisplatin. Further, genomic heterogeneity and unique tumor cell sub-populations with reduced sensitivities to cisplatin play a role in its effectiveness within a site of tumor growth. Being exposed to sub-lethal doses will induce changes in gene expression that contribute to the tumour cell's ability to survive and eventually contribute to the selective pressures leading to cisplatin resistance...
2016: PloS One
https://www.readbyqxmd.com/read/26921632/loss-of-the-lim-only-protein-fhl2-impairs-inflammatory-reaction-and-scar-formation-after-cardiac-ischemia-leading-to-better-hemodynamic-performance
#19
Diane Goltz, Kanishka Hittetiya, Heidrun Gevensleben, Jutta Kirfel, Linda Diehl, Rainer Meyer, Reinhard Büttner
AIMS: The pathogenesis of myocardial ischemia-reperfusion injury (MI/R) involves an inflammatory response. Since the four-and-a-half LIM domain-containing protein 2 (Fhl2) has been observed to modulate immune cell migration, we aimed to study the consequences of Fhl2(-/-) under MI/R with respect to immune reaction, scar formation, and hemodynamic performance. MATERIAL AND METHODS: In a closed chest model of 1h MI/R, immune cell invasion of phagocytic monocytes was characterized by flow cytometry and immunohistochemistry...
April 15, 2016: Life Sciences
https://www.readbyqxmd.com/read/26861258/aging-associated-dna-methylation-changes-in-middle-aged-individuals-the-young-finns-study
#20
L Kananen, S Marttila, T Nevalainen, J Jylhävä, N Mononen, M Kähönen, O T Raitakari, T Lehtimäki, M Hurme
BACKGROUND: Chronological aging-associated changes in the human DNA methylome have been studied by multiple epigenome-wide association studies (EWASs). Certain CpG sites have been identified as aging-associated in multiple studies, and the majority of the sites identified in various studies show common features regarding location and direction of the methylation change. However, as a whole, the sets of aging-associated CpGs identified in different studies, even with similar tissues and age ranges, show only limited overlap...
2016: BMC Genomics
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