Identification of a RAD51B enhancer variant for susceptibility and progression to glioma

Cancer Cell International

Research

Wenshen Xu¹  Xi Shi²  Shu Zhang²  Lian Dai³  Liming Huang⁴  Meiqin Chen⁴  Danfang Yan⁵ 

[1] Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, 350005, Fuzhou, China;Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, 350005, Fuzhou, China;Department of Medical Oncology, The First Affiliated Hospital, Fujian Medical University, 350005, Fuzhou, China;Department of Medicine, The Third Affiliated People’s Hospital, Fujian University of Traditional Chinese Medicine, #363 Guobin Road, 350108, Fuzhou, China;Department of Oncology, The Affiliated People’s Hospital, Fujian University of Traditional Chinese Medicine, #602 Bayiqizhong Road, 350004, Fuzhou, China;Department of Radiation Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, Hangzhou, China;

关键词: Glioma;    RAD51B;    Enhancer;    Genetic variation;    Susceptibility;    Progression;   

DOI  :  10.1186/s12935-023-03100-8

 received in 2023-02-26, accepted in 2023-10-14,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundRAD51B plays a significant role in homologous recombination-mediated repair of DNA double-strand breaks. Many enhancer variants are involved in cancer development and progression. However, the significance of enhancer variants of RAD51B in glioma susceptibility and progression remains unclear.MethodsA case–control study consisting of 1056 individuals was conducted to evaluate the associations of enhancer variants of RAD51B with glioma susceptibility and progression. Sequenom MassARRAY technology was used for genotyping. The function of enhancer variants was explored by biochemical assays.ResultsA significantly decreased risk of glioma was associated with rs6573816 GC genotype compared with rs6573816 GG genotype (OR = 0.66, 95% CI 0.45–0.97; P = 0.034). Multivariable Cox regression revealed that rs6573816 was significantly associated with glioma progression in a sex-dependent manner. Worse PFS was found in the male patients with high grade glioma carrying rs6573816 GC or CC genotype (HR = 2.28, 95% CI 1.14–4.57; P = 0.020). The rs6573816 C allele repressed enhancer activity by affecting transcription factor POU2F1 binding, which resulted in lower expression of RAD51B. Remarkably attenuated expression of RAD51B was observed following POU2F1 knockdown. Consistently, positive correlation between the expression of POU2F1 and RAD51B was found in lymphoblastic cells and glioma tissues.ConclusionsThese results indicate that an enhancer variant of RAD51B rs6573816 influences enhancer activity by changing a POU2F1 binding site and confers susceptibility and progression to glioma.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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