Functional SNP in 3′-UTR MicroRNA-Binding Site of<i>ZNF350</i>Confers Risk for Age-Related Cataract

Gu, Shanshan; Ren, Han; Zhang, Guowei; Kang, Lihua; Yang, Mei; Guan, Huaijin

doi:10.1002/humu.23073

Cited by 20 publications

(14 citation statements)

References 55 publications

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“…SNPs located at miRNA binding sites can effect the base pairing between miRNA and target mRNA, which further affect miRNA-mediated genes expression. A number of studies have proved that SNPs mapping to miRNA binding sites can affect the expression level of target genes, thus involved in initiation and progression of disease [40–43]. Rs3181385 is a SNP located at miRNA binding site of ADCY4 gene, in the present study there is a bordering significant association with the risk of NSCLC.…”

Section: Discussionsupporting

confidence: 55%

Multiple functional SNPs in differentially expressed genes modify risk and survival of non-small cell lung cancer in chinese female non-smokers

Fang

Yin

et al. 2017

Oncotarget

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DNA genotype can affect gene expression, and gene expression can influence the onset and progression of diseases. Here we conducted a comprehensive study, we integrated analysis of gene expression profile and single nucleotide polymorphism (SNP) microarray data in order to scan out the critical genetic changes that participate in the onset and development of non-small cell lung cancer (NSCLC). Gene expression profile datasets were downloaded from the GEO database. Firstly, differentially expressed genes (DEGs) between NSCLC samples and adjacent normal samples were identified. Next, by STRING database, protein-protein interaction (PPI) network was constructed. At the same time, hub genes in PPI network were identified. Then, some functional SNPs in hub genes that may affect gene expression have been annotated. Finally, we carried a study to explore the relationship between functional SNPs and NSCLC risk and overall survival in Chinese female non-smokers. A total of 488 DEGs were identified in our study. There are 29 proteins with a higher degree of connectivity in the PPI network, including FOS, IL6 and MMP9. By using database annotation, we got 8 candidate functional SNPs that may affect the expression level of hub proteins. In the case-control study, we found that rs4754-T allele, rs959173-C allele and rs2239144-G allele were the protective allele of NSCLC risk. In dominant model, rs4754-CT+TT genotype were associated with a shorter survival time. In general, our study provides a novel research direction in the field of multi-omic data integration, and helps us find some critical genetic changes in disease.

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Section: Discussionsupporting

confidence: 55%

Multiple functional SNPs in differentially expressed genes modify risk and survival of non-small cell lung cancer in chinese female non-smokers

Fang

Yin

et al. 2017

Oncotarget

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“…Assuming that individuals have similar levels of hsa-miR-3912-5p in lens tissue, NEIL2 in those with the C allele would have a stronger interaction with hsa-miR-3912-5p, resulting in lower NEIL2 expression and DNA repair capability than in the individuals carrying the T allele. The extent of DNA breaks in peripheral lymphocytes was significantly higher in ARCs regardless of genotype (24,25). Individuals with different genotypes showed various damage levels in their peripheral lymphocytes (41).…”

Section: Discussionmentioning

confidence: 91%

“…Furthermore, studies have documented that SNPs in the 39UTR of the miRNA target gene [e.g., SNPs within miRNA (miRSNPs)] could interfere with the mRNA stability itself (22,23). Our previous studies found that miRSNPs in the ataxia-telangiesctasia mutated and zinc finger protein 350 genes could alter binding ability to corresponding miRNAs and ultimately affect ARC pathogenesis (24,25).…”

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confidence: 99%

A variant in a microRNA binding site in NEIL2 3′UTR confers susceptibility to age‐related cataracts

et al. 2019

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DNA damage in lens cells is considered a critical trigger for the onset of age‐related cataracts (ARCs). Among DNA repair pathways, the base excision repair (BER) pathway is responsible for mending single‐strand breaks in DNA. In this case‐control study with 993 ARC cases and 993 healthy controls, we genotyped 9 single‐nucleotide polymorphisms (SNPs) within microRNA (miRNA) regions of 6 BER pathway genes and examined their associations with ARC susceptibility. We identified rs4639:T > C in the Nei‐like DNA glycosylase 2 (NEIL2) gene as significantly associated with ARCs. Individuals carrying different rs4639 alleles had distinct NEIL2 expression in lens capsule tissues from ARC cases and controls. Bioinformatics predicts that the rs4639 T allele could disrupt hsa‐miR‐3912‐5p binding. The results of the luciferase reporter assay were in concordance with this prediction. This study has added more evidence that SNP‐modified posttranscriptional gene regulation by miRNA might be a potential pathogenic mechanism of ARCs. SNPs potentially affecting miRNA binding to the 3′UTR of BER pathway genes could contribute to discrepant disease susceptibility. NEIL2‐rs4639T was strongly associated with a protective role in ARCs. This protective role might be fulfilled by maintaining normal expression of NEIL2 in the mediation of disrupted binding of rs4639T with hsa‐miR‐3912‐5p. A further study to generate model systems (cell lines or animal models) with NEIL2 variants is warranted. The results provide 2 molecular targets (e.g., NEIL2 and hsa‐miR‐3912‐5p) for intervention strategies of ARC in the future.—Kang, L., Zou, X., Zhang, G., Xiang, J., Wang, Y., Yang, M., Chen, X., Wu, J., Guan, H. A variant in a microRNA binding site in NEIL23′UTR confers susceptibility to age‐related cataract. FASEB J. 33, 10469–10476 (2019). http://www.fasebj.org

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“…The highest of the free energy change is 10.9 kcal/mol about rs2278414 in ZNF350 3′ UTR and has-miR-21-3p. And rs2278414: C > T was significantly associated with age-related cataract (ARC) risk, which associated with DNA double-strand break repair (DSBR) and nucleotide excision repair (NER) pathway [29]. …”

Section: Resultsmentioning

confidence: 99%

An Integrating Approach for Genome-Wide Screening of MicroRNA Polymorphisms Mediated Drug Response Alterations

Wang

Jiang

et al. 2017

International Journal of Genomics

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MicroRNAs (miRNAs) are a class of evolutionarily conserved small noncoding RNAs, ~22 nt in length, and found in diverse organisms and play important roles in the regulation of mRNA translation and degradation. It was shown that miRNAs were involved in many key biological processes through regulating the expression of targets. Genetic polymorphisms in miRNA target sites may alter miRNA regulation and therefore result in the alterations of the drug targets. Recent studies have demonstrated that SNPs in miRNA target sites can affect drug efficiency. However, there are still a large number of specific genetic variants related to drug efficiency that are yet to be discovered. We integrated large scale of genetic variations, drug targets, gene interaction networks, biological pathways, and seeds region of miRNA to identify miRNA polymorphisms affecting drug response. In addition, harnessing the abundant high quality biological network/pathways, we evaluated the cascade distribution of tarSNP impacts. We showed that the predictions can uncover most of the known experimentally supported cases as well as provide informative candidates complementary to existing methods/tools. Although there are several existing databases predicting the gain or loss of targeting function of miRNA mediated by SNPs, such as PolymiRTS, miRNASNP, MicroSNiPer, and MirSNP, none of them evaluated the influences of tarSNPs on drug response alterations. We developed a user-friendly online database of this approach named Mir2Drug.

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Functional SNP in 3′-UTR MicroRNA-Binding Site ofZNF350Confers Risk for Age-Related Cataract

Cited by 20 publications

References 55 publications

Multiple functional SNPs in differentially expressed genes modify risk and survival of non-small cell lung cancer in chinese female non-smokers

Multiple functional SNPs in differentially expressed genes modify risk and survival of non-small cell lung cancer in chinese female non-smokers

A variant in a microRNA binding site in NEIL2 3′UTR confers susceptibility to age‐related cataracts

An Integrating Approach for Genome-Wide Screening of MicroRNA Polymorphisms Mediated Drug Response Alterations

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