scholarly journals The regulatory roles and mechanisms of the transcription factor FOXF2 in human diseases

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10845
Author(s):  
Qiong Wu ◽  
Wei Li ◽  
Chongge You
Keyword(s):  
Transcription Factor ◽  
Human Diseases ◽  
Aberrant Expression ◽  
Regulatory Pathways ◽  
Forkhead Box ◽  
Pathological Conditions ◽  
Functional Development ◽  
Transcription Factor Regulation ◽  
The Relationship

Many studies have focused on the relationship between transcription factors and a variety of common pathological conditions, such as diabetes, stroke, and cancer. It has been found that abnormal transcription factor regulation can lead to aberrant expression of downstream genes, which contributes to the occurrence and development of many diseases. The forkhead box (FOX) transcription factor family is encoded by the FOX gene, which mediates gene transcription and follow-up functions during physiological and pathological processes. FOXF2, a member of the FOX transcription family, is expressed in various organs and tissues while maintaining their normal structural and functional development during the embryonic and adult stages. Multiple regulatory pathways that regulate FOXF2 may also be controlled by FOXF2. Abnormal FOXF2 expression induced by uncontrollable regulatory signals mediate the progression of human diseases by interfering with the cell cycle, proliferation, differentiation, invasion, and metastasis. FOXF2 manipulates downstream pathways and targets as both a pro-oncogenic and anti-oncogenic factor across different types of cancer, suggesting it may be a new potential clinical marker or therapeutic target for cancer. However, FOXF2’s biological functions and specific roles in cancer development remain unclear. In this study, we provide an overview of FOXF2’s structure, function, and regulatory mechanisms in the physiological and pathological conditions of human body. We also discussed the possible reasons why FOXF2 performs the opposite function in the same types of cancer.

scholarly journals Forkhead Box Transcription Factor Regulation and Lipid Accumulation by Hepatitis C Virus

2014 ◽  
Vol 88 (8) ◽  
pp. 4195-4203 ◽  
Author(s):  
S. K. Bose ◽  
H. Kim ◽  
K. Meyer ◽  
N. Wolins ◽  
N. O. Davidson ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Lipid Accumulation ◽  
Forkhead Box ◽  
Transcription Factor Regulation

scholarly journals Transcription factor regulation as a mechanism of confounding effects between distinct human traits

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 1349
Author(s):  
Milos Pjanic ◽  
Clint L. Miller ◽  
Thomas Quertermous
Keyword(s):  
Type 2 Diabetes ◽  
Transcription Factor ◽  
Genetic Variants ◽  
Human Diseases ◽  
Upstream Region ◽  
Hair Color ◽  
Human Populations ◽  
Genome Wide Association Studies ◽  
Transcription Factor Regulation

Genome-wide association studies (GWAS) to date have discovered thousands of genetic variants linked to human diseases and traits, which hold the potential to unravel the mechanisms of complex phenotypes. However, given that the majority of these associated variants reside in non-coding genomic regions, their predicted cis and trans-regulatory functions remain largely undefined. Here we show that correlation between human diseases and traits can follow geographical distribution of human populations, and that the underlying mechanism is at least partly genetically based. We report two Type 2 Diabetes (T2D) GWAS variants (rs7903146 and rs12255372) in the TCF7L2 locus that regulate expression in skin tissues but not lymphoblastoid or adipose tissues, of the KITLG gene that encodes an important regulator of melanogenesis and light hair color in European populations. We also report extensive binding events of TCF7L2 protein in the promoter region, immediate upstream region and first intron of the KITLG gene, which supports a trans-interaction between TCF7L2 and KITLG. We further show that both light hair color and T2D genetic variants are correlated with geographic latitude. Taken together, our observations suggest that natural variation in transcription factor loci in European human populations may be an underlying and confounding factor for the geographical correlation between human phenotypes, such as type 2 diabetes and light hair color. We postulate that transcription factor regulation may confound the correlation between seemingly diverse human traits. Furthermore, our findings demonstrate the importance of dissecting the genomic architecture of GWAS loci using multiple genetic and genomic datasets.

scholarly journals The Role of Forkhead Box Protein M1 in Breast Cancer Progression and Resistance to Therapy

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Raya Saba ◽  
Alhareth Alsayed ◽  
James P. Zacny ◽  
Arkadiusz Z. Dudek
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Regulatory Pathways ◽  
Forkhead Box ◽  
Epidermal Growth

The Forkhead box M1 (FOXM1) is a transcription factor that has been implicated in normal cell growth and proliferation through control of cell cycle transition and mitotic spindle. It is implicated in carcinogenesis of various malignancies where it is activated by either amplification, increased stability, enhanced transcription, dysfunction of regulatory pathways, or activation of PI3K/AKT, epidermal growth factor receptor, Raf/MEK/MAPK, and Hedgehog pathways. This review describes the role of FOXM1 in breast cancer. This includes how FOXM1 impacts on different subtypes of breast cancer, that is, luminal/estrogen receptor positive (ER+), expressing human epidermal growth factor receptor 2 (HER2), basal-like breast cancer (BBC), and triple negative breast cancer (TNBC). The review also describes different tested preclinical therapeutic strategies targeting FOXM1. Developing clinically applicable therapies that specifically inhibit FOXM1 activity is a logical next step in biomarker-driven approaches against breast cancer but will not be without its challenges due to the unique properties of this transcription factor.

scholarly journals Tolerance to Hypoxia Is Promoted by FOXO Regulation of the Innate Immunity Transcription Factor NF-κB/Relish in Drosophila

Genetics ◽  
2020 ◽  
Vol 215 (4) ◽  
pp. 1013-1025 ◽  
Author(s):  
Elizabeth C. Barretto ◽  
Danielle M. Polan ◽  
Amy N. Beevor-Potts ◽  
Byoungchun Lee ◽  
Savraj S. Grewal
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Innate Immune ◽  
Hypoxia Tolerance ◽  
Dependent Manner ◽  
Low Oxygen ◽  
Hypoxia Exposure ◽  
Forkhead Box ◽  
Pathological Conditions

Exposure of tissues and organs to low oxygen (hypoxia) occurs in both physiological and pathological conditions in animals. Under these conditions, organisms have to adapt their physiology to ensure proper functioning and survival. Here, we define a role for the transcription factor Forkhead Box-O (FOXO) as a mediator of hypoxia tolerance in Drosophila. We find that upon hypoxia exposure, FOXO transcriptional activity is rapidly induced in both larvae and adults. Moreover, we see that foxo mutant animals show misregulated glucose metabolism in low oxygen and subsequently exhibit reduced hypoxia survival. We identify the innate immune transcription factor, NF-κB/Relish, as a key FOXO target in the control of hypoxia tolerance. We find that expression of Relish and its target genes is increased in a FOXO-dependent manner in hypoxia, and that relish mutant animals show reduced survival in hypoxia. Together, these data indicate that FOXO is a hypoxia-inducible factor that mediates tolerance to low oxygen by inducing immune-like responses.

scholarly journals A Pan-Cancer Analysis of Transcription Factor Forkhead Box O-3: FOXO3

2021 ◽  
Author(s):  
Guiyang cai ◽  
Jiacheng Li ◽  
Qing Yang ◽  
Wei Sun
Keyword(s):  
Transcription Factor ◽  
Cancer Associated Fibroblasts ◽  
Promoting Effect ◽  
Clinical Prognosis ◽  
Statistical Correlations ◽  
Forkhead Box ◽  
Tumor Mutational Burden ◽  
The Relationship ◽  
Pan Cancer

Abstract Background: Although available cell - or animal- based evidence supports the relationship between transcription factor FOXO3 and cancers, so far, there has been no pan-cancer analysis of FOXO3. Methods: We thus first carry on a pan-cancer analysis of FOXO3 across multiple tumors via several online websites based on the datasets of TCGA, including statistical correlations of FOXO3 expression with clinical prognosis, protein phosphorylation, cancer-associated fibroblasts infiltration, tumor mutational burden, and relevant cellular pathway. Results: FOXO3 was usually as an anti-tumor gene in KIRC, BLCA, CESC, UVM, LUAD and BRCA cancers, while a higher level of FOXO3 may have a certain cancer-promoting effect. As FOXO3 usually played a cancer-promoting role in ERα- BRCA but in ERα+ BRCA played an anti-tumor role, which may be due to transcription factor ERα translocating FOXO3 to the cytoplasm to weaken the transcription activity of FOXO3. FOXO3 activates autophagy related genes through transcription to maintain the occurrence of basal autophagy when basal autophagy is inhibited. However, FOXO3 can also induce apoptosis through transcription of pro-apoptotic genes if autophagy inhibition persists. The expression of phosphorylated FOXO3 protein at different sites may also affect its transcriptional activity by changing its shuttle between nucleus and cytoplasm. Therefore, When we analyze the functions of FOXO3 in a specific type of cancer, we should combine with the expression of FOXO3, the alteration status of FOXO3, the overall phosphorylation status of FOXO3, the basic autophagy status, the expression levels of ERα, SIRT1, CBP, FKBP5, RERE and SMAD4, and cancer-associated fibroblasts subtype, even consider the KRAS mutation, P53 mutation or non-genetic factors which can influence the functions of cancer-associated fibroblasts in the specific type of cancer. Conclusions: Our first pan-cancer study has provided a relatively comprehensive understanding of the role of FOXO3 in different tumors, and will give some help and enlightenment to later researchers who study the role of FOXO3 in various cancers.

scholarly journals SRMDAP: SimRank and Density-Based Clustering Recommender Model for miRNA-Disease Association Prediction

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Xiaoying Li ◽  
Yaping Lin ◽  
Changlong Gu ◽  
Zejun Li
Keyword(s):  
Cross Validation ◽  
Computational Method ◽  
Human Diseases ◽  
Excellent Performance ◽  
Aberrant Expression ◽  
Experimental Identification ◽  
Density Based Clustering ◽  
Disease Associations ◽  
Leave One Out ◽  
The Relationship

Aberrant expression of microRNAs (miRNAs) can be applied for the diagnosis, prognosis, and treatment of human diseases. Identifying the relationship between miRNA and human disease is important to further investigate the pathogenesis of human diseases. However, experimental identification of the associations between diseases and miRNAs is time-consuming and expensive. Computational methods are efficient approaches to determine the potential associations between diseases and miRNAs. This paper presents a new computational method based on the SimRank and density-based clustering recommender model for miRNA-disease associations prediction (SRMDAP). The AUC of 0.8838 based on leave-one-out cross-validation and case studies suggested the excellent performance of the SRMDAP in predicting miRNA-disease associations. SRMDAP could also predict diseases without any related miRNAs and miRNAs without any related diseases.

scholarly journals Prostaglandin E2 Induces Fibroblast Growth Factor 9 via EP3-Dependent Protein Kinase Cδ and Elk-1 Signaling

2006 ◽  
Vol 26 (22) ◽  
pp. 8281-8292 ◽  
Author(s):  
Pei-Chin Chuang ◽  
H. Sunny Sun ◽  
Tsung-Ming Chen ◽  
Shaw-Jenq Tsai
Keyword(s):  
Transcription Factor ◽  
Growth Factor ◽  
Protein Kinase ◽  
Fibroblast Growth Factor ◽  
Signaling Pathway ◽  
Human Diseases ◽  
Prostaglandin E ◽  
Fibroblast Growth ◽  
Aberrant Expression ◽  
Protein Kinase Cδ

ABSTRACT Fibroblast growth factor 9 (FGF-9) is a potent mitogen that controls the proper development of many tissues and organs. In contrast, aberrant expression of FGF-9 also results in the evolution of many human diseases, such as cancers and endometriosis. Despite its vital function being reported, the cellular and molecular mechanisms responsible for the regulation of FGF-9 expression are mostly unknown. We report here that prostaglandin E2 (PGE2) induces expression of FGF-9, which promotes endometriotic stromal cell proliferation, through the EP3 receptor-activated protein kinase Cδ (PKCδ) signaling pathway. Activation of PKCδ leads to phosphorylation of ERK1/2, and the transcription factor Elk-1 thereby promotes transcription of FGF-9. Two Elk-1 cis-binding sites located at nucleotides −1324 to −1329 and −1046 to −1051 of the human FGF-9 promoter are identified as crucial for mediating PGE2 actions. Collectively, we demonstrate, for the first time, that PGE2 can directly induce FGF-9 expression via a novel signaling pathway involving EP3, PKCδ, and a member of the ETS domain-containing transcription factor superfamily in primary human endometriotic stromal cells. Our findings may also provide a molecular framework for considering roles for PGE2 in FGF-9-related embryonic development and/or human diseases.

Relationship between Thyroglobulin and Tumor Detectabilily with Thallium-201 in Differentiated Thyroid Cancer

2000 ◽  
Vol 39 (01) ◽  
pp. 10-15 ◽  
Author(s):  
S. P. Müller ◽  
Ch. Reiners ◽  
A. Bockisch ◽  
Katja Brandt-Mainz
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Roc Analysis ◽  
Tsh Suppression ◽  
Significant Difference ◽  
Test Specificity ◽  
The Relationship ◽  
Tumor Scintigraphy ◽  
Tsh Stimulation

Summary Aim: Tumor scintigraphy with 201-TICI is an established diagnostic method in the follow-up of differentiated thyroid cancer. We investigated the relationship between thyroglobulin (Tg) level and tumor detectability. Subject and methods: We analyzed the scans of 122 patients (66 patients with proven tumor). The patient population was divided into groups with Tg above (N = 33) and below (N = 33) 5 ng/ml under TSH suppression or above (N = 33) and below (N = 33) 50 ng/ml under TSH stimulation. Tumor detectability was compared by ROC-analysis (True-Positive-Fraction test, specificity 90%). Results: There was no significant difference (sensitivity 75% versus 64%; p = 0.55) for patients above and below 5 ng/ml under TSH suppression and a just significant difference (sensitivity 80% versus 58%; p = 0.04) for patients above and below 50 ng/ml under TSH stimulation. In 18 patients from our sample with tumor, Tg under TSH suppression was negative, but 201-TICI-scan was able to detect tumor in 12 patients. Conclusion: Our results demonstrate only a moderate dependence of tumor detectability on Tg level, probably without significant clinical relevance. Even in patients with slight Tg elevation 201-TICI scintigraphy is justified.

A Decade of Disparities in Diabetes Technology Use and HbA1c in Pediatric Type 1 Diabetes: A Trans-Atlantic Comparison

2020 ◽  
Author(s):  
Ananta Addala ◽  
Marie Auzanneau ◽  
Kellee Miller ◽  
Werner Maier ◽  
Nicole Foster ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Technology Use ◽  
Hemoglobin A1c ◽  
Diabetes Technology ◽  
Design And Methods ◽  
Relationship Of ◽  
The Relationship ◽  
Pediatric Type 1 Diabetes

<b>Objective:</b> As diabetes technology use in youth increases worldwide, inequalities in access may exacerbate disparities in hemoglobin A1c (HbA1c). We hypothesized an increasing gap in diabetes technology use by socioeconomic status (SES) would be associated with increased HbA1c disparities. <p> </p> <p><b>Research Design and Methods: </b>Participants aged <18 years with diabetes duration ≥1 year in the Type 1 Diabetes Exchange (T1DX, US, n=16,457) and Diabetes Prospective Follow-up (DPV, Germany, n=39,836) registries were categorized into lowest (Q1) to highest (Q5) SES quintiles. Multiple regression analyses compared the relationship of SES quintiles with diabetes technology use and HbA1c from 2010-2012 and 2016-2018. </p> <p> </p> <p><b>Results: </b>HbA1c was higher in participants with lower SES (in 2010-2012 & 2016-2018, respectively: 8.0% & 7.8% in Q1 and 7.6% & 7.5% in Q5 for DPV; and 9.0% & 9.3% in Q1 and 7.8% & 8.0% in Q5 for T1DX). For DPV, the association between SES and HbA1c did not change between the two time periods, whereas for T1DX, disparities in HbA1c by SES increased significantly (p<0.001). After adjusting for technology use, results for DPV did not change whereas the increase in T1DX was no longer significant.</p> <p> </p> <p><b>Conclusions: </b>Although causal conclusions cannot be drawn, diabetes technology use is lowest and HbA1c is highest in those of the lowest SES quintile in the T1DX and this difference for HbA1c broadened in the last decade. Associations of SES with technology use and HbA1c were weaker in the DPV registry. </p>

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