Krüppel-Like Factors

Pollak, Nina M.; Hoffman, Matthew; Goldberg, Ira J.; Drosatos, Konstantinos

doi:10.1016/j.jacbts.2017.09.001

Cited by 100 publications

(46 citation statements)

References 243 publications

(372 reference statements)

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“…Vik-1 belongs to the Krüppel-like factors (KLFs) protein family, which regulate the metabolic pathways across various tissues. KLFs have been shown to interact with the components of atherosclerosis pathogenesis and have also been linked to metabolic abnormalities, including obesity and diabetes mellitus (Pollak et al, 2018). In line with our findings from KEGG enrichment analysis of co-expressed genes of ZNF655, Zhao et al (2016) constructed a genetic network based on gene-gene interactions and revealed that pathways involved in Alzheimer's disease, non-alcoholic fatty liver disease, and Huntington's disease were also associated with CAD risk.…”

Section: Discussionsupporting

confidence: 74%

Exome-Wide Association Study Reveals Several Susceptibility Genes and Pathways Associated With Acute Coronary Syndromes in Han Chinese

et al. 2020

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Genome-wide association studies have identified more than 150 susceptibility loci for coronary artery disease (CAD); however, there is still a large proportion of missing heritability remaining to be investigated. This study sought to identify population-based genetic variation associated with acute coronary syndromes (ACS) in individuals of Chinese Han descent. We proposed a novel strategy integrating a well-developed risk prediction model into control selection in order to lower the potential misclassification bias and increase the statistical power. An exome-wide association analysis was performed for 1,669 ACS patients and 1,935 healthy controls. Promising variants were further replicated using the existing in silico dataset. Additionally, we performed gene-and pathway-based analyses to investigate the aggregate effect of multiple variants within the same genes or pathways. Although none of the association signals were consistent across studies after Bonferroni correction, one promising variant, rs10409124 at STRN4, showed potential impact on ACS in both European and East Asian populations. Gene-based analysis explored four genes (ANXA7, ZNF655, ZNF347, and ZNF750) that showed evidence for association with ACS after multiple test correction, and identification of ZNF655 was successfully replicated by another dataset. Pathway-based analysis revealed that 32 potential pathways might be involved in the pathogenesis of ACS. Our study identified several candidate genes and pathways associated with ACS. Future studies are needed to further validate these findings and explore these genes and pathways as potential therapeutic targets in ACS.

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Section: Discussionsupporting

confidence: 74%

Exome-Wide Association Study Reveals Several Susceptibility Genes and Pathways Associated With Acute Coronary Syndromes in Han Chinese

et al. 2020

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“…Several groups have described various approaches to identify all of the members of the SP/KLF family in human and mouse genomes, and the effects of these proteins in more detail [ 4 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. As shown in Figure 1 , the protein-binding domains within the protein structures of KLF Group 1 (KLF 3, 8, and 12) serve as transcriptional repressors through their interaction with the C-terminal binding protein (CtBP).…”

Section: Sp/klf Familymentioning

confidence: 99%

KLF10 as a Tumor Suppressor Gene and Its TGF-β Signaling

Memon

Lee

2018

Cancers

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Krüppel-like factor 10 (KLF10), originally named TGF-β (Transforming growth factor beta) inducible early gene 1 (TIEG1), is a DNA-binding transcriptional regulator containing a triple C2H2 zinc finger domain. By binding to Sp1 (specificity protein 1) sites on the DNA and interactions with other regulatory transcription factors, KLF10 encourages and suppresses the expression of multiple genes in many cell types. Many studies have investigated its signaling cascade, but other than the TGF-β/Smad signaling pathway, these are still not clear. KLF10 plays a role in proliferation, differentiation as well as apoptosis, just like other members of the SP (specificity proteins)/KLF (Krüppel-like Factors). Recently, several studies reported that KLF10 KO (Knock out) is associated with defects in cell and organs such as osteopenia, abnormal tendon or cardiac hypertrophy. Since KLF10 was first discovered, several studies have defined its role in cancer as a tumor suppressor. KLF10 demonstrate anti-proliferative effects and induce apoptosis in various carcinoma cells including pancreatic cancer, leukemia, and osteoporosis. Collectively, these data indicate that KLF10 plays a significant role in various biological processes and diseases, but its role in cancer is still unclear. Therefore, this review was conducted to describe and discuss the role and function of KLF10 in diseases, including cancer, with a special emphasis on its signaling with TGF-β.

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“…Insulin is a hormone produced in the pancreas that helps maintain the blood glucose homeostasis (47)(48)(49). Several members of the KLF family members, including KLF14, have confirmed roles in the regulation of insulin sensitivity [reviewed in (50)]. Yang et al used high-fat diet (HFD)-fed mice and leptin receptor-deficient (db/db) mice that have impaired insulin sensitivity and showed that there is significant down-regulation of Klf14 expression in skeletal muscle (51).…”

Section: The Role Of Klf14 In Cardiometabolic Disordersmentioning

confidence: 99%

“…Inhibition of SK1 resulted in accumulation of the lipid second messenger ceramides in liver cancer cells (54), while elevated muscle ceramides have been associated with muscle insulin resistance in obese humans (55). As such, some of the KLF14-mediated metabolic phenotypes may be attributed to regulation of lipid signaling via dysregulation of SK1 (50,53). Below we summarize the studies that elucidated the role of KLF14 in metabolically active organs.…”

Section: The Role Of Klf14 In Cardiometabolic Disordersmentioning

confidence: 99%

Transcription Factor KLF14 and Metabolic Syndrome

Yang

Civelek

2020

Front. Cardiovasc. Med.

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Metabolic syndrome (MetSyn) is a combination of metabolic abnormalities that lead to the development of cardiovascular disease (CVD) and Type 2 Diabetes (T2D). Although various criteria for defining MetSyn exist, common abnormalities include abdominal obesity, elevated serum triglyceride, insulin resistance, and blood glucose, decreased high-density lipoprotein cholesterol (HDL-C), and hypertension. MetSyn prevalence has been increasing with the rise of obesity worldwide, with significantly higher prevalence in women compared with men and in Hispanics compared with Whites. Affected individuals are at a higher risk of developing T2D (5-fold) and CVD (2-fold). Heritability estimates for individual components of MetSyn vary between 40 and 70%, suggesting a strong contribution of an individual's genetic makeup to disease pathology. The advent of nextgeneration sequencing technologies has enabled large-scale genome-wide association studies (GWAS) into the genetics underlying MetSyn pathogenesis. Several such studies have implicated the transcription factor KLF14, a member of the Krüpple-like factor family (KLF), in the development of metabolic diseases, including obesity, insulin resistance, and T2D. How KLF14 regulates these metabolic traits and increases the risk of developing T2D, atherosclerosis, and liver dysfunction is still unknown. There have been some debate and controversial results with regards to its expression profile and functionality in various tissues, and a systematic review of current knowledge on KLF14 is lacking. Here, we summarize the research progress made in understanding the function of KLF14 and describe common attributes of its biochemical, physiological, and pathophysiological roles. We also discuss the current challenges in understanding the role of KLF14 in metabolism and provide suggestions for future directions.

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Krüppel-Like Factors

Cited by 100 publications

References 243 publications

Exome-Wide Association Study Reveals Several Susceptibility Genes and Pathways Associated With Acute Coronary Syndromes in Han Chinese

Exome-Wide Association Study Reveals Several Susceptibility Genes and Pathways Associated With Acute Coronary Syndromes in Han Chinese

KLF10 as a Tumor Suppressor Gene and Its TGF-β Signaling

Transcription Factor KLF14 and Metabolic Syndrome

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