POLE2

Last update 08 May 2025

Basic Info

Synonyms

DNA polymerase epsilon 2, accessory subunit, DNA polymerase epsilon subunit 2, DNA polymerase epsilon subunit B

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Introduction

Accessory component of the DNA polymerase epsilon complex (PubMed:10801849). Participates in DNA repair and in chromosomal DNA replication (By similarity).

100 Clinical Results associated with POLE2

100 Translational Medicine associated with POLE2

0 Patents (Medical) associated with POLE2

111

Literatures (Medical) associated with POLE2

01 Jul 2025·Cellular Signalling

GINS4 silencing mediates hepatocellular cancer cell proliferation, cycle and ferroptosis through POLE2

Article

Author: Wang, Congyu ; Song, Rui ; Xu, Zhe ; Yao, Jinni ; Yang, Huaicheng ; Zeng, Xiangrui ; Zhang, Zheng ; Yuan, Meng ; Liao, Heqiang

BACKGROUNDGINS4 has been identified as a regulator associated with multiple types of cancers. However, the effects of GINS4 on hepatocellular carcinoma (HCC) have not been reported.METHODSGINS4 expression in HCC was evaluated utilizing UALCAN database. The relationship between the expression of GINS4 and the survival probability of HCC patients was analyzed using Kaplan-Meier Plotter. Cell viability was evaluated by CCK8 assay and EDU assay. qRT-PCR and western blot were performed to examine GINS4 expression. The level of cell cycle was measured by flow cytometry and western blot. Fe²⁺ level and ferroptosis-related proteins were measured by corresponding kits and western blot. Lipid peroxidation was explored by C11 BODIPY 581/591 probe. STRING database and HDOCK database were performed to predict the binding of GINS4 to POLE2. Immunofluorescence and western blotting was adopted for assessing cell autophagy and mTOR signaling pathway. Ki67 and GPX4 levels were measured by immunohistochemistry. The expression levels of POLE2/PI3K/AKT were assessed by western blot.RESULTSThe data indicated that GINS4 expression was upregulated in HCC. Knockdown of GINS4 alleviated the proliferation and cycle and promoted ferroptosis of HuH7 cells. GINS4 was proved to bind to POLE2 and the silencing of GINS4 inhibited the expression of POLE2. GINS4 knockdown accelerated ferroptosis in HuH7 cells. POLE2 overexpression reversed the influences of GINS4 silencing on proliferation and cycle, and also ferroptosis. In addition, interference with GINS4 suppressed the activation of PI3K/AKT signaling via POLE2. In vivo experiments illustrated that GINS4 deletion suppressed HCC tumor growth, increased the GPX4 expression and restrained the Ki67 level, as well as reducing POLE2/PI3K/AKT signaling.CONCLUSIONGINS4 silencing suppressed proliferation and cycle while promoted ferroptosis in HCC cells by regulating PI3K/AKT signaling via binding to POLE2.

01 Jun 2025·Comparative Biochemistry and Physiology Part D: Genomics and Proteomics

Transcriptome analysis reveals the DNA replication genes response to Vibrio anguillarum and NNV infection in Jinhu grouper (Epinephelus fuscoguttatus♀ × Epinephelus tukulal♂)

Article

Author: Li, Zhentong ; Ren, Gehui ; Zhang, Yazhuo ; Liu, Jia ; Tian, Yongsheng ; Duan, Huimin

Vibrio anguillarum acts as an infectious agent in the aquaculture industry that causes a fatal hemolytic septicaemic disease in fish and shellfish. Viral nervous necrosis (VNN) disease seriously impacts the healthy development of the aquaculture industry. While the detrimental effects of V. anguillarum and NNV have been widely researched on freshwater and marine fish, whether they affect DNA replication in fish is unclear. In this study, we used Jinhu grouper as a model to investigate the influence of V. anguillarum and NNV on their DNA replication. By RNA-seq analysis in conjunction with gene set enrichment analysis, we found a significant upregulation of genes related to DNA replication in the liver and spleen of the Jinhu grouper after V. anguillarum infection while a prominent downregulation of genes related to DNA replication in the brain of the Jinhu grouper after NNV infection. We identified 27, 29 and 18 key genes involved in DNA replication that may respond to V. anguillarum and NNV infection and selected and identified six DNA replication genes (pole, pole2, pold1, pola1, pcna and mcm2). In addition, our results indicated that these genes exhibit tissue-specific expression patterns, with an increasing pattern of expression when V. anguillarum infected and a decreasing pattern when NNV infected. These results may provide valuable understanding on the underlying mechanisms of V. anguillarum and NNV infection in fish.

01 May 2025·Current Medicinal Chemistry

Multitargeted Docking, DFT-Based Optimisation, Pharmacokinetics, and MD Simulation Reveal 6-Oxidopamine HBr as a Multitargeted Inhibitor of Cervical Cancer Proteins

Article

Author: Alharthi, Afaf Awwadh ; Mashraqi, Mutaib M. ; Gharib, Amal F. ; Alghamdi, Youssef Saeed ; Alsalmi, Ohud

Background:Cervical cancer originates in the cervix, the lower part of the uterus, and results from the uncontrolled growth of abnormal cervical cells, forming malignant tumours. It poses a major global health challenge, calling for innovative drug design strategies to enhance treatment outcomes.Method:In this study, we have screened the FDA-approved drug library against four proteins, MCM10, MCM6, DNA polymerase epsilon subunit-2, and TBK1, which are essential for DNA replication, DNA repair, and cellular signalling pathways, which are dysregulated in cervical cancer cells, leading to uncontrolled growth. We have used the multisampling algorithms for screening using HTVS, SP, and XP docking; identified 6- oxidopamine HBr (C8H12BrNO3), which is used to create a model of Parkinson’s disease in animals, and obtained the docking score ranging from -5.057 to -8.871 Kcal/mol. The poses were filtered with MM\GBSA score ranging from -21.67 to -27.63 Kcal/mol. We performed QM-based DFT and pharmacokinetics studies and compared them with the standard values, suggesting that the compound can be used in cervical cancer proteins.Result:The P-L complex’s interaction fingerprints have resulted in the most interacting residues, 4THR, 4SER, and 4LYS, showing the compound’s interaction pattern.Conclusion:Further, the stability of 6-oxidopamine HBr in complex with each protein was evaluated with 100 ns MD simulation in the SPC water model in a neutralised state to analyse the deviation, fluctuations, and intermolecular interactions that have proven the compound to have a better inhibitory effect against each protein and that it can be used for cervical cancer; however, experimental validation is suggested before human use.

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POLE2

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