Potential Regulatory SNPs in the
            <i>ATXN7L3B</i>
            and
            <i>KRT15</i>
            Genes are Associated with Gender-Specific Colorectal Cancer Risk

Leberfarb, Elena Yu; Degtyareva, Arina O.; Brusentsov, Ilya I.; Максимов, В. Н.; Воевода, М. И.; Autenshlus, A. I.; Morozov, D. V.; Соколов, А. В.; Merkulova, T. I.

doi:10.2217/pme-2019-0059

Cited by 6 publications

(4 citation statements)

References 54 publications

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“…Both lncRNAs formed a ceRNA relationship with the mRNA ATXN7L3B and formed ceRNA relationships with some other mRNAs, respectively. ATXN7L3B have been confirmed to be associated with an increased risk of colorectal cancer ( Leberfarb et al, 2020 ), and cytoplasmic ATXN7L3B interfered with the nuclear functions of the SAGA deubiquitinase module ( Li et al, 2016 ). The SAGA complex was composed of two enzymatic modules, which house histone acetyltransferase (HAT) and deubiquitinase (DUB) activities.…”

Section: Resultsmentioning

confidence: 99%

Pan-Cancer Methylated Dysregulation of Long Non-coding RNAs Reveals Epigenetic Biomarkers

Zhao

Guo

Zhang

et al. 2022

Front. Cell Dev. Biol.

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Different cancer types not only have common characteristics but also have their own characteristics respectively. The mechanism of these specific and common characteristics is still unclear. Pan-cancer analysis can help understand the similarities and differences among cancer types by systematically describing different patterns in cancers and identifying cancer-specific and cancer-common molecular biomarkers. While long non-coding RNAs (lncRNAs) are key cancer modulators, there is still a lack of pan-cancer analysis for lncRNA methylation dysregulation. In this study, we integrated lncRNA methylation, lncRNA expression and mRNA expression data to illuminate specific and common lncRNA methylation patterns in 23 cancer types. Then, we screened aberrantly methylated lncRNAs that negatively regulated lncRNA expression and mapped them to the ceRNA relationship for further validation. 29 lncRNAs were identified as diagnostic biomarkers for their corresponding cancer types, with lncRNA AC027601 was identified as a new KIRC-associated biomarker, and lncRNA ACTA2-AS1 was regarded as a carcinogenic factor of KIRP. Two lncRNAs HOXA-AS2 and AC007228 were identified as pan-cancer biomarkers. In general, the cancer-specific and cancer-common lncRNA biomarkers identified in this study may aid in cancer diagnosis and treatment.

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Section: Resultsmentioning

confidence: 99%

Pan-Cancer Methylated Dysregulation of Long Non-coding RNAs Reveals Epigenetic Biomarkers

Zhao

Guo

Zhang

et al. 2022

Front. Cell Dev. Biol.

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“…Genotyping of CRC patients and healthy controls according to six of these polymorphisms demonstrated that rs590352 of ATXN7L3B gene was associated with CRC in men and rs4796672 of KRT15 gene, with CRC in women. In addition, the analysis of haplotypes shows that rs2072580, located in the promoter region common for the ISCU and SART3 genes, can be also associated with CRC [ 174 ].…”

Section: Rsnps On a Genome-wide Scalementioning

confidence: 99%

Regulatory SNPs: Altered Transcription Factor Binding Sites Implicated in Complex Traits and Diseases

Degtyareva

Antontseva

Merkulova

2021

IJMS

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The vast majority of the genetic variants (mainly SNPs) associated with various human traits and diseases map to a noncoding part of the genome and are enriched in its regulatory compartment, suggesting that many causal variants may affect gene expression. The leading mechanism of action of these SNPs consists in the alterations in the transcription factor binding via creation or disruption of transcription factor binding sites (TFBSs) or some change in the affinity of these regulatory proteins to their cognate sites. In this review, we first focus on the history of the discovery of regulatory SNPs (rSNPs) and systematized description of the existing methodical approaches to their study. Then, we brief the recent comprehensive examples of rSNPs studied from the discovery of the changes in the TFBS sequence as a result of a nucleotide substitution to identification of its effect on the target gene expression and, eventually, to phenotype. We also describe state-of-the-art genome-wide approaches to identification of regulatory variants, including both making molecular sense of genome-wide association studies (GWAS) and the alternative approaches the primary goal of which is to determine the functionality of genetic variants. Among these approaches, special attention is paid to expression quantitative trait loci (eQTLs) analysis and the search for allele-specific events in RNA-seq (ASE events) as well as in ChIP-seq, DNase-seq, and ATAC-seq (ASB events) data.

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“…Another 30 rSNPs have been implicated in colorectal cancer with the help of data from the International Cancer Ge nome Consortium (ICGC) (Seshagiri et al, 2012). Genotyping of patients with colorectal cancer and healthy individuals for six of these SNPs has revealed an association of rs590352, rs4796672, and rs2072580 with this disease (Leberfarb et al, 2020). A correlation with breast cancer has been found for rs2072580 (Degtyareva et al, 2020).…”

mentioning

confidence: 99%

Human-genome single nucleotide polymorphisms affecting transcription factor binding and their role in pathogenesis

Antontseva,

Degtyareva,

Korbolina

et al. 2023

Vestn. VOGiS

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Single nucleotide polymorphisms (SNPs) are the most common type of variation in the human genome. The vast majority of SNPs identified in the human genome do not have any effect on the phenotype; however, some can lead to changes in the function of a gene or the level of its expression. Most SNPs associated with certain traits or pathologies are mapped to regulatory regions of the genome and affect gene expression by changing transcription factor binding sites. In recent decades, substantial effort has been invested in searching for such regulatory SNPs (rSNPs) and understanding the mechanisms by which they lead to phenotypic differences, primarily to individual differences in susceptibility to di seases and in sensitivity to drugs. The development of the NGS (next-generation sequencing) technology has contributed not only to the identification of a huge number of SNPs and to the search for their association (genome-wide association studies, GWASs) with certain diseases or phenotypic manifestations, but also to the development of more productive approaches to their functional annotation. It should be noted that the presence of an association does not allow one to identify a functional, truly disease-associated DNA sequence variant among multiple marker SNPs that are detected due to linkage disequilibrium. Moreover, determination of associations of genetic variants with a disease does not provide information about the functionality of these variants, which is necessary to elucidate the molecular mechanisms of the development of pathology and to design effective methods for its treatment and prevention. In this regard, the functional analysis of SNPs annotated in the GWAS catalog, both at the genome-wide level and at the level of individual SNPs, became especially relevant in recent years. A genome-wide search for potential rSNPs is possible without any prior knowledge of their association with a trait. Thus, mapping expression quantitative trait loci (eQTLs) makes it possible to identify an SNP for which – among transcriptomes of homozygotes and heterozygotes for its various alleles – there are differences in the expression level of certain genes, which can be located at various distances from the SNP. To predict rSNPs, approaches based on searches for allele-specific events in RNA-seq, ChIP-seq, DNase-seq, ATAC-seq, MPRA, and other data are also used. Nonetheless, for a more complete functional annotation of such rSNPs, it is necessary to establish their association with a trait, in particular, with a predisposition to a certain pathology or sensitivity to drugs. Thus, approaches to finding SNPs important for the development of a trait can be categorized into two groups: (1) starting from data on an association of SNPs with a certain trait, (2) starting from the determination of allele-specific changes at the molecular level (in a transcriptome or regulome). Only comprehensive use of strategically different approaches can considerably enrich our knowledge about the role of genetic determinants in the molecular mechanisms of trait formation, including predisposition to multifactorial diseases.

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Potential Regulatory SNPs in the ATXN7L3B and KRT15 Genes are Associated with Gender-Specific Colorectal Cancer Risk

Cited by 6 publications

References 54 publications

Pan-Cancer Methylated Dysregulation of Long Non-coding RNAs Reveals Epigenetic Biomarkers

Pan-Cancer Methylated Dysregulation of Long Non-coding RNAs Reveals Epigenetic Biomarkers

Regulatory SNPs: Altered Transcription Factor Binding Sites Implicated in Complex Traits and Diseases

Human-genome single nucleotide polymorphisms affecting transcription factor binding and their role in pathogenesis

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