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Review
. 2025 Jul 21:13:1612329.
doi: 10.3389/fcell.2025.1612329. eCollection 2025.

Research progress on the role of the NEIL family in cancer

Yinghan Chen #  1 , Muyun Ma #  2 , Aixue Zou #  3 , Xinjia Wang  1 , Weiwei Dong  4
Affiliations
Review

Research progress on the role of the NEIL family in cancer

Yinghan Chen et al. Front Cell Dev Biol. .

Abstract

Cancer is the primary cause of death worldwide. Cancer occurrence and progression are closely associated with DNA damage repair. DNA glycosylase were the first enzymes to initiate base excision repair, and the Nei-like DNA glycosylase (NEIL) family has attracted increasing attention as an important component of DNA glycosylases. Here, we introduce the role of the NEIL family in the malignant biological behaviors of cancer, including cell proliferation, chemoradiotherapy resistance, invasion and migration, apoptosis, and stemness. Mechanisms affecting the expression of the NEIL protein family range from the transcriptional level and mRNA editing to the level of post-translational modification. Additionally, we emphasize the different functions of the NEIL family in various malignancies and present useful information that supports the hypothesis that the NEIL family could be a potential target in the treatment and diagnosis of various cancers.

Keywords: DNA; NEIL; cancer; glycosylases; malignancy; treatment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The structure of NEIL family.
FIGURE 2
FIGURE 2
Common upstream regulatory mechanisms, targets and cellular functions of NEIL family. In the transcriptional level, promoter methylation, the combination of several proteins and ncRNAs may affect the NEIL family expression. Additionally, ADAR1 edits NEIL1 mRNA after transcription. After translation, a variety of protein modifications such as acetylation, deacetylation, phosphorylation, and ubiquitination affect the activity of NEIL protein. NEIL family also influence the malignant biological behaviors of cancer in several ways. Reducing cell cycle arrest and repairing telomeres are the main approaches to accelerate cell proliferation. In chemotherapy resistance, NEIL1 competes with ICL DNA repair pathway to maintains cisplatin cytotoxicity. NEIL2 promotes ROS repair, besides, loss of NEIL2 leads to disruption of the G1-S phase transition. NEIL3 promoting EMT pathway and ATM/ATR pathway, but inhibiting WRNIP. NEIL family also play a vital role in invasion and migration, apoptosis, and stemness.
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