Roles of NUCKS1 in Diseases: Susceptibility, Potential Biomarker, and Regulatory Mechanisms

Huang, Pengru; Cai, Yujie; Zhao, Bin; Cui, Lili

doi:10.1155/2018/7969068

Cited by 24 publications

(22 citation statements)

References 65 publications

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“…NUCKS1 is similar to the high mobility group (HMG) family, which dominates chromatin remodeling and regulates gene transcription [7]. NUCKS1 plays a significant role in various diseases as susceptibility or potential marker and involve in several regulatory mechanisms [8-12] Noticeably, NUCKS1 involves in cell growth and proliferation as well as in DNA repair [13]. Using genome wide Association Studies (GWAS) it was found that NUCKS1 is a susceptibility gene for many diseases and a single disease can be associated with multiple SNPs of NUCKS1.…”

Section: Introductionmentioning

confidence: 99%

Functional association between NUCKS1 gene and Parkinson disease: A potential susceptibility biomarker

Singh¹,

Seth²

2019

Bioinformation

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Several Genome Wide Association Studies (GWASs) have reported that PARK16 gene locus possibly regulate the risk of Parkinson's disease (PD). It contains functionally interesting candidate genes for PD, regulated by number of SNPs. In present study rs823093 polymorphism in NUCKS1 gene has been evaluated as significant performer in PD though its mechanism is not yet known. Here various regulatory and functional analyses were performed using computational tools and information from databases. The rs823093 variant was predicted to locate in enhancer histone marks in blood and have strong transcription in various parts of brain, heart, kidney and liver. PhenoScanner (a database of human genotype-phenotype associations) identified significant associations of this variant with many other diseases and phenotypic conditions as well. Gene expression analysis shows significant association with multiple human tissues and multiple genes together with NUCKS1. Further, the post mortem brain samples showed diverse expressions of NUCKS1 gene in PD patients compared to healthy samples. Besides, the metabolite analysis shows significant association with serotonin a known neurotransmitter, and other 15 metabolites. In addition, NUCKS1 also showed co-expression with ZNF43 and PLIN1 genes involved in cell cycle regulation presume their association in PD. Thus, these data links NUCKS1 gene as a potential disease susceptibility biomarker for PD.

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Section: Introductionmentioning

confidence: 99%

Functional association between NUCKS1 gene and Parkinson disease: A potential susceptibility biomarker

Singh¹,

Seth²

2019

Bioinformation

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“…Lastly, rs823114, with the 7th lowest p-value (4.35x10-09), and a less significant SNP, rs7536483, are located in the promoter of NUCKS1 (Nuclear casein kinase and cyclin-dependent kinase substrate 1). NUCKS1 is a chromatin-associated protein with a role in the DNA damage response, DNA repair, metabolism, and inflammatory and immune responses, but its overall function is still unknown [36]. Other than rs4889599, we observed that these SNPs are located in ATAC-peaks that are flanked by H3K27ac ChIP-seq peaks.…”

Section: Finding Candidate Functional Snpsmentioning

confidence: 77%

Parkinson’s Disease Genetic Risk Evaluation in Microglia Highlights Autophagy and Lysosomal Genes

Booms

Pierce

Coetzee

2020

Preprint

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Genome-wide association studies (GWAS) have uncovered thousands of single nucleotide polymorphisms (SNPs) that are associated with Parkinsons disease (PD) risk. The functions of most of these SNPs, including the cell type they influence, and how they affect PD etiology remain largely unknown. To identify functional SNPs, we aligned PD risk SNPs within active regulatory regions of DNA in microglia, a cell type implicated in PD development. Out of 6,749 SNPs of interest from the most recent PD GWAS metanalysis, 73 were located in open regulatory chromatin as determined by both ATAC-seq and H3K27ac ChIP-seq. We highlight a subset of SNPs that are favorable candidates for further mechanistic studies. These SNPs are located in regulatory DNA at the SLC50A1, SNCA, BAG3, FBXL19, SETD1A, and NUCKS1 loci. A network analysis of the genes with risk SNPs in their promoters, implicated substance transport, involving autophagy and lysosomal genes. Our study provides a more focused set of risk SNPs and their associated risk genes as candidates for further follow-up studies, which will help identify mechanisms in microglia that increase the risk for PD.

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“…Following the TSP pathway is NUCKS1, this gene codes for nuclear casein kinase and cyclin-dependent kinase substrate 1 [ 77 ]. NUCKS1 is a nuclear protein, highly conserved in vertebrates [ 78 ]. It is expressed in most tissues and experiments in rats have shown that its expression increases during the initial stages of embryonic development in brain and liver [ 77 ].…”

Section: Discussionmentioning

confidence: 99%

“…Qiu et al [ 79 ] reported that in the embryonic development, NUCKS1 appears to be a marker for migrating cells of the neural crests. NUCKS1 has been shown to be important for homologous recombination DNA damage response [ 80 ] and to play a role in inflammatory immune response [ 78 ]. It is interesting to note that the NUCKS1 product is also used by the HIV-1 for the viral transcription of its genetic material [ 81 ] and has been reported as a biomarker for some cancer [ 82, 83 ].…”

Section: Discussionmentioning

confidence: 99%

A Selection of Important Genes and Their Correlated Behavior in Alzheimer’s Disease

Cruz-Rivera

Pérez‐Morales

Santiago

et al. 2018

JAD

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In 2017, approximately 5 million Americans were living with Alzheimer’s disease (AD), and it is estimated that by 2050 this number could increase to 16 million. In this study, we apply mathematical optimization to approach microarray analysis to detect differentially expressed genes and determine the most correlated structure among their expression changes. The analysis of GSE4757 microarray dataset, which compares expression between AD neurons without neurofibrillary tangles (controls) and with neurofibrillary tangles (cases), was casted as a multiple criteria optimization (MCO) problem. Through the analysis it was possible to determine a series of Pareto efficient frontiers to find the most differentially expressed genes, which are here proposed as potential AD biomarkers. The Traveling Sales Problem (TSP) model was used to find the cyclical path of maximal correlation between the expression changes among the genes deemed important from the previous stage. This leads to a structure capable of guiding biological exploration with enhanced precision and repeatability. Ten genes were selected (FTL, GFAP, HNRNPA3, COX1, ND2, ND3, ND4, NUCKS1, RPL41, and RPS10) and their most correlated cyclic structure was found in our analyses. The biological functions of their products were found to be linked to inflammation and neurodegenerative diseases and some of them had not been reported for AD before. The TSP path connects genes coding for mitochondrial electron transfer proteins. Some of these proteins are closely related to other electron transport proteins already reported as important for AD.

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Roles of NUCKS1 in Diseases: Susceptibility, Potential Biomarker, and Regulatory Mechanisms

Cited by 24 publications

References 65 publications

Functional association between NUCKS1 gene and Parkinson disease: A potential susceptibility biomarker

Functional association between NUCKS1 gene and Parkinson disease: A potential susceptibility biomarker

Parkinson’s Disease Genetic Risk Evaluation in Microglia Highlights Autophagy and Lysosomal Genes

A Selection of Important Genes and Their Correlated Behavior in Alzheimer’s Disease

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