Nei Endonuclease VIII-Like1 (NEIL1) Inhibits Apoptosis of Human Colorectal Cancer Cells

Xue, Weiwei; Liu, Yongcheng; Xin, Ningning; Miao, Jiyu; Du, Juan; Wang, Yu; Shi, Haiyan; Wei, Yameng; Zhang, Huahua; Chen, Yani; Gao, Yi; Li, Dan; Feng, Yun; Yan, Jing; Zhang, Jing; Hou, Ni; Huang, Chen; Han, Jianbo

doi:10.1155/2020/5053975

Cited by 4 publications

(2 citation statements)

References 13 publications

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“…Our Western blot analysis on lymphoblastoid cells from the index of FAP104 with the c.506G>A variant revealed strikingly increased amount of NEIL1 protein, and we hypothesize that the c.506G>A variant is mutagenic due to the accumulation of functionally defective protein. Our result would comply with a possible oncogenic role proposed for NEIL1 in some studies ( 39 ).…”

Section: Discussionsupporting

confidence: 93%

Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents

Olkinuora

Mayordomo²,

Kauppinen³

et al. 2022

Front. Oncol.

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Recently, biallelic germline variants of the DNA glycosylase genes MUTYH and NTHL1 were linked to polyposis susceptibility. Significant fractions remain without a molecular explanation, warranting searches for underlying causes. We used exome sequencing to investigate clinically well-defined adenomatous polyposis cases and families from Finland (N=34), Chile (N=21), and Argentina (N=12), all with known susceptibility genes excluded. Nine index cases (13%) revealed germline variants with proven or possible pathogenicity in the DNA glycosylase genes, involving NEIL1 (mono- or biallelic) in 3 cases, MUTYH (monoallelic) in 3 cases, NTHL1 (biallelic) in 1 case, and OGG1 (monoallelic) in 2 cases. NTHL1 was affected with the well-established, pathogenic c.268C>T, p.(Gln90Ter) variant. A recurrent heterozygous NEIL1 c.506G>A, p.(Gly169Asp) variant was observed in two families. In a Finnish family, the variant occurred in trans with a truncating NEIL1 variant (c.821delT). In an Argentine family, the variant co-occurred with a genomic deletion of exons 2 – 11 of PMS2. Mutational signatures in tumor tissues complied with biological functions reported for NEIL1. Our results suggest that germline variants in DNA glycosylase genes may occur in a non-negligible proportion of unexplained colon polyposis cases and may predispose to tumor development.

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Section: Discussionsupporting

confidence: 93%

Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents

Olkinuora

Mayordomo²,

Kauppinen³

et al. 2022

Front. Oncol.

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“…The latest research on human colorectal cancer (CRC) shows that silence of NEIL1 in two CRC (HCT116 and SW480) cell lines promoted cell apoptosis through the caspase‐9 signaling pathway. On the contrary, overexpression of NEIL1 in two cell lines got opposite phenomenon (Xue et al, 2020 ). All of those results indicated the importance of NEIL1 in BER pathway, however, we noticed that complications during cancer radiotherapy are also deserved our concern.…”

Section: Discussionmentioning

confidence: 99%

Genetic variations in DNA repair gene NEIL1 associated with radiation pneumonitis risk in lung cancer patients

Zheng

et al. 2021

Molec Gen & Gen Med

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Background Radiation pneumonitis (RP) is a common side effect in lung cancer patients who received radiotherapy. Our previous study found genetic variations in DNA repair gene NEIL1 may be a predictor of RP in patients with esophageal cancer. So, we hypothesis genetic variations in NEIL1 gene could affect the risk of RP in lung cancer patients following radiotherapy. Methods Genetic variations rs4462560 G>C and rs7402844 C>G in NEIL1 gene were genotyped in 174 lung cancer patients received radio(chemo)therapy. Luciferase assay, real‐time PCR and Western blot were used to access the effect of the variants on NEIL1 in HELF and HEF cell lines which were transfected with plasmids containing rs4462560 G>C and rs7402844 C>G. Results Patients with rs4462560 CC genotype had a lower risk of RP grade ≥2 than GG genotype. Compared with the CC genotype, rs7402844 GG genotype was associated with an increased RP grade ≥2 risk. What is more, rs4462560 G decreased the relative luciferase activity of NEIL1 gene promoter compared with the negative control in vitro, while rs4462560 C can increase the relative luciferase activity. The mRNA and protein level of the NEIL1 gene in rs4462560 G were lower than rs4462560 C. Conclusions Genetic variants of NEIL1 are associated with RP risk through regulation of NEIL1 expression and serve as independent biomarkers for prediction of RP in patients treated with thoracic radiotherapy.

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Decoding the Role of NEIL1 Gene in DNA Repair and Lifespan: A Literature Review with Bioinformatics Analysis

Mohajeri Khorasani,

Raghibi,

Haj Mohammad Hassani

et al. 2024

Advanced Biology

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Longevity, the length of an organism's lifespan, is impacted by environmental factors, metabolic processes, and genetic determinants. The base excision repair (BER) pathway is crucial for maintaining genomic integrity by repairing oxidatively modified base lesions. Nei‐like DNA Glycosylase 1 (NEIL1), part of the BER pathway, is vital in repairing oxidative bases in G‐rich DNA regions, such as telomeres and promoters. Hence, in this comprehensive review, it have undertaken a meticulous investigation of the intricate association between NEIL1 and longevity. The analysis delves into the multifaceted aspects of the NEIL1 gene, its various RNA transcripts, and the diverse protein isoforms. In addition, a combination of bioinformatic analysis is conducted to identify NEIL1 mutations, transcription factors, and epigenetic modifications, as well as its lncRNA/pseudogene/circRNA‐miRNA‐mRNA regulatory network. The findings suggest that the normal function of NEIL1 is a significant factor in human health and longevity, with defects in NEIL1 potentially leading to various cancers and related syndromes, Alzheimer's disease, obesity, and diabetes.

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Nei Endonuclease VIII-Like1 (NEIL1) Inhibits Apoptosis of Human Colorectal Cancer Cells

Cited by 4 publications

References 13 publications

Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents

Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents

Genetic variations in DNA repair gene NEIL1 associated with radiation pneumonitis risk in lung cancer patients

Decoding the Role of NEIL1 Gene in DNA Repair and Lifespan: A Literature Review with Bioinformatics Analysis

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