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Zhongwei Jia, Fangning Wan, Yao Zhu, Guohai Shi, Hailiang Zhang, Bo Dai, Dingwei Ye
Previous studies have demonstrated that several members of the Forkhead-box (FOX) family of genes are associated with tumor progression and metastasis. The objective of the current study was to screen candidate FOX family genes identified from analysis of molecular networks in clear cell renal cell carcinoma (ccRCC). The expression of FOX family genes as well as FOX family-associated genes was examined, and Kaplan-Meier survival analysis was performed in The Cancer Genome Atlas (TCGA) cohort (n=525). Patient characteristics, including sex, age, tumor diameter, laterality, tumor-node-metastasis, tumor grade, stage, white blood cell count, platelet count, the levels of hemoglobin, overall survival (OS) and disease-free survival (DFS), were collected for univariate and multivariate Cox proportional hazards ratio analyses...
June 2018: Oncology Letters
Jia Ma, Yanwei Lu, Sheng Zhang, Yan Li, Jing Huang, Zhongyuan Yin, Jinghua Ren, Kai Huang, Li Liu, Kunyu Yang, Gang Wu, Shuangbing Xu
Aberrant expression of FOXN2, a member of the Forkhead box transcription factors, has been found in several types of cancer. However, the underlying mechanisms of FOXN2 deregulation in tumorigenesis remain largely unknown. Here, we find that FOXN2 binds to and is ubiquitinated by β-Trcp ubiquitin ligase and RSK2 kinase for degradation. Furthermore, we demonstrate that the Ser365 and Ser369 sites in a conserved DSGYAS motif are critical for the degradation of FOXN2 by β-Trcp and RSK2. Moreover, gain-of-function and loss-of-function studies show that FOXN2 impairs cell proliferation in vitro and in vivo and enhances the radiosensitivity of lung cancer...
February 2, 2018: Cell Death and Differentiation
Stefan Nagel, Claudia Pommerenke, Corinna Meyer, Maren Kaufmann, Roderick A F MacLeod, Hans G Drexler
To identify novel cancer-related genes targeted by copy number alterations, we performed genomic profiling of T-cell acute lymphoblastic leukemia (T-ALL) cell lines. In 3/8, we identified a shared deletion at chromosomal position 2p16.3-p21. Within the minimally deleted region, we recognized several candidate tumor suppressor (TS) genes, including FBXO11 and FOXN2. An additional deletion at chromosome 14q23.2-q32.11 included FOXN3, highlighting this class of FOX genes as potential TS. Quantitative expression analyses of FBXO11, FOXN2, and FOXN3 confirmed reduced transcript levels in the identified cell lines...
September 2017: Leukemia & Lymphoma
K Hardy, F Wu, W Tu, A Zafar, T Boulding, R McCuaig, C R Sutton, A Theodoratos, S Rao
Epithelial-to-mesenchymal transition (EMT) is physiological in embryogenesis and wound healing but also associated with the formation of cancer stem cells (CSCs). Many EMT signaling pathways are implicated in CSC formation, but the precise underlying mechanisms of CSC formation remain elusive. We have previously demonstrated that PKC is critical for EMT induction and CSC formation in inducible breast EMT/CSC models. Here, we used formaldehyde-assisted isolation of regulatory elements-sequencing (FAIRE-seq) to investigate DNA accessibility changes after PKC activation and determine how they influence EMT and CSC formation...
2016: Nucleus
Emily Robertson, Christina Perry, Rachel Doherty, Srinivasan Madhusudan
BACKGROUND: The Forkhead box transcription factor (FOX) family plays an essential role in embryogenesis, especially during brain development. Our hypothesis is that de-regulation of FOX genes may contribute to aggressive tumor biology and therapy resistance in patients with glioblastoma multiforme (GBM). MATERIALS AND METHODS: Univariate and multivariate analyses were performed to evaluate prognostic significance of transcript levels of 31 FOX genes in a test set of GBM patients (n=191) and validated them in The Cancer Genome Atlas (TCGA) cohort comprising of 508 adult cases of GBM...
May 2015: Cancer Genomics & Proteomics
Taeheon Lee, Dong-Hyun Shin, Seoae Cho, Hyun Sung Kang, Sung Hoon Kim, Hak-Kyo Lee, Heebal Kim, Kang-Seok Seo
The increasing importance of meat quality has implications for animal breeding programs. Research has revealed much about the genetic background of pigs, and many studies have revealed the importance of various genetic factors. Since meat quality is a complex trait which is affected by many factors, consideration of the overall phenotype is very useful to study meat quality. For integrating the phenotypes, we used principle component analysis (PCA). The significant SNPs refer to results of the GRAMMAR method against PC1, PC2 and PC3 of 14 meat quality traits of 181 Duroc pigs...
March 2014: Asian-Australasian Journal of Animal Sciences
Lindsay R Saunders, David R McClay
Epithelial-mesenchymal transition (EMT) is a fundamental cell state change that transforms epithelial to mesenchymal cells during embryonic development, adult tissue repair and cancer metastasis. EMT includes a complex series of intermediate cell state changes including remodeling of the basement membrane, apical constriction, epithelial de-adhesion, directed motility, loss of apical-basal polarity, and acquisition of mesenchymal adhesion and polarity. Transcriptional regulatory state changes must ultimately coordinate the timing and execution of these cell biological processes...
April 2014: Development
Yan J Jiang, Daniel D Bikle
Accumulating evidence strongly suggests a protective role of vitamin D signaling against chemical and UVR-induced skin cancer formation. However, the mechanism remains largely unknown. Recently, the emerging role of long, non-coding RNA (lncRNA) as a hallmark of cancer has become better appreciated. LncRNAs are mRNA-like transcripts ranging in length from 200 bases to 100kb lacking significant open reading frames, which are involved in a broad spectrum of tumorigenic/metastatic processes. In this study we profiled 90 well-annotated mouse lncRNAs from cultured mouse keratinocytes after deleting the vitamin D receptor (VDR) (∼90%) vs...
October 2014: Journal of Steroid Biochemistry and Molecular Biology
Ho Kyung Rho, David R McClay
Early development requires well-organized temporal and spatial regulation of transcription factors that are assembled into gene regulatory networks (GRNs). In the sea urchin, an endomesoderm GRN model explains much of the specification in the endoderm and mesoderm prior to gastrulation, yet some GRN connections remain incomplete. Here, we characterize FoxN2/3 in the primary mesenchyme cell (PMC) GRN state. Expression of foxN2/3 mRNA begins in micromeres at the hatched blastula stage and then is lost from micromeres at the mesenchyme blastula stage...
March 2011: Development
Immo A Hansen, Douglas H Sieglaff, James B Munro, Shin-Hong Shiao, Josefa Cruz, Iris W Lee, John M Heraty, Alexander S Raikhel
Forkhead-box (Fox) genes encode a family of transcription factors defined by a 'winged helix' DNA-binding domain. In this study we aimed to identify Fox factors that are expressed within the fat body of the yellow fever mosquito Aedes aegypti, and determine whether any of these are involved in the regulation of mosquito yolk protein gene expression. The Ae. aegypti genome contains 18 loci that encode putative Fox factors. Our stringent cladistic analysis has profound implications for the use of Fox genes as phylogenetic markers...
September 2007: Insect Biochemistry and Molecular Biology
Maximilian Schuff, Antje Rössner, Cornelia Donow, Walter Knöchel
Using RT-PCR and in situ hybridisation, we have analysed the temporal and spatial expression patterns of Xenopus Fox genes of subclass N. By screening cDNA libraries and by RT-PCR using embryonic RNA and primers derived from EST analyses, we could isolate FoxN2, FoxN4, FoxN5 and different isoforms of FoxN3. FoxN2 and FoxN3 transcripts were found during all developmental stages including early cleavage and tailbud stages. FoxN5 transcripts were only present at early cleavage stages, while FoxN4 expression began after midblastula transition...
2006: International Journal of Developmental Biology
Masuko Katoh, Masaru Katoh
Forkhead-box (FOX) superfamily genes are implicated in carcinogenesis through gene amplification, retroviral integration and chromosomal translocation. FOX superfamily genes within the human genome are classified into 17 or 18 families, designated FOX# (# is alphabet A-Q or R). FOXN1, FOXN2 (HTLF), FOXN3 (CHES1), FOXN4, FOXN5 (FOXR1) and FOXN6 (FOXR2) genes constitute the FOXN gene family. Here, we characterized human FOXN4 gene by using bioinformatics. FOXN4 gene at human chromosome 12q24.12 was found to encode three isoforms...
November 2004: International Journal of Molecular Medicine
Masuko Katoh, Masaru Katoh
Human Forkhead-box (FOX) gene family consists of at least 43 members, including FOXA1, FOXA2, FOXA3, FOXB1, FOXC1, FOXC2, FOXD1, FOXD2, FOXD3, FOXD4, FOXD5 (FOXD4L1), FOXD6 (FOXD4L3), FOXE1, FOXE2, FOXE3, FOXF1, FOXF2, FOXG1 (FOXG1B), FOXH1, FOXI1, FOXJ1, FOXJ2, FOXJ3, FOXK1, FOXK2, FOXL1, FOXL2, FOXM1, FOXN1, FOXN2 (HTLF), FOXN3 (CHES1), FOXN4, FOXN5 (FOXR1), FOXN6 (FOXR2), FOXO1 (FOXO1A), FOXO2 (FOXO6), FOXO3 (FOXO3A), FOXO4 (MLLT7), FOXP1, FOXP2, FOXP3, FOXP4, and FOXQ1. FOXE3-FOXD2 (1p33), FOXQ1-FOXF2-FOXC1 (6p25...
November 2004: International Journal of Oncology
Masuko Katoh, Masaru Katoh
Forkhead-box (FOX) transcription factors are implicated in carcinogenesis through gene amplification, retroviral integration, or chromosomal translocation. FOXN1, FOXN2 (HTLF), FOXN3 (CHES1), FOXN4 and FOXN5 (FOXR1) constitute the FOXN family. Here, we identified and characterized human FOXN6 (FOXR2) and rodent Foxn6 (Foxr2) orthologs by using bioinformatics. Human FOXN6 gene was identified within human genome sequence RP11-167P23 (AL159987.19), mouse Foxn6 gene within mouse genome sequence RP23-180D16 (AL672293...
July 2004: International Journal of Oncology
Masuko Katoh, Masaru Katoh
Forkhead-box (FOX) genes are implicated in embryogenesis through transcriptional regulation depending on SHH-GLI pathway, TGF-beta pathway etc., and also in carcinogenesis through gene amplification, retroviral integration and chromosomal translocation. FOXN1, FOXN2 (HTLF), FOXN3 (CHES1) and FOXN4 constitute the FOXN family. Here, we identified and characterized the FOXN5 gene, a novel member of FOXN gene family, by using bioinformatics. IMAGE5167039 (BC028191.1) was the representative cDNA derived from human FOXN5 gene...
May 2004: International Journal of Oncology
Carla Tribioli, Raymond F Robledo, Thomas Lufkin
The fork head domain-containing gene family (Fox) comprises over 20 members in mammals and is defined by a conserved 110 amino-acid motif containing a winged helix structure DNA-binding domain. The members of this gene family have been implicated as key regulators of embryogenesis, cell cycling, cell lineage restriction and cancer. The Foxn2 gene (Ches1) is expressed in postgastrulation embryos in multiple tissues that serve as important signaling centers as well as end-stage-differentiated cell types that arise from different germ layers of the developing embryo...
October 2002: Mechanisms of Development
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