Zhao Yangjing, Wang Hui, Zhou Jingdong, Shao Qixiang
Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China.
Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212002, China.
Cancers (Basel). 2022 May 23;14(10):2560. doi: 10.3390/cancers14102560.
As the first identified selenoprotein, glutathione peroxidase 1 (GPX1) is a widely and abundantly expressed antioxidant enzyme. GPX1 utilizes glutathione as a substrate to catalyze hydrogen peroxide, lipid peroxide, and peroxynitrite, thereby reducing intracellular oxidative stress. The GPX1 gene is regulated at transcriptional, post-transcriptional, and translational levels. Numerous case-control studies and meta-analyses have assessed the association between a functional genetic polymorphism of the GPX1 gene, named Pro198Leu (rs1050450 C>T), and cancer susceptibility in different populations. GPX1 polymorphism has type-specific effects as a candidate marker for cancer risk, but the association between GPX1 variants and cancer susceptibility remains controversial in different studies. GPX1 is abnormally elevated in most types of cancer but has complex dichotomous roles as tumor suppressor and promoter in different cancers. GPX1 can participate in various signaling pathways to regulate tumor biological behaviors, including cell proliferation, apoptosis, invasion, immune response, and chemoresistance. In this review, we comprehensively summarize the controversial associations between GPX1 polymorphism and cancer risks and further discuss the relationships between the aberrant expressions of GPX1 and tumorigenesis. Further studies are needed to elucidate the clinical significance of GPX1 as a potential prognostic biomarker and novel therapeutic target in various malignancies.
作为首个被鉴定出的硒蛋白，谷胱甘肽过氧化物酶1（GPX1）是一种广泛且大量表达的抗氧化酶。GPX1利用谷胱甘肽作为底物来催化过氧化氢、脂质过氧化物和过氧亚硝酸盐，从而减轻细胞内的氧化应激。GPX1基因在转录、转录后和翻译水平受到调控。众多病例对照研究和荟萃分析评估了GPX1基因的一种功能性基因多态性，即Pro198Leu（rs1050450 C>T），与不同人群癌症易感性之间的关联。GPX1多态性作为癌症风险的候选标志物具有类型特异性效应，但在不同研究中，GPX1变异与癌症易感性之间的关联仍存在争议。GPX1在大多数类型的癌症中异常升高，但在不同癌症中作为肿瘤抑制因子和促进因子具有复杂的双重作用。GPX1可参与多种信号通路来调节肿瘤生物学行为，包括细胞增殖、凋亡、侵袭、免疫反应和化疗耐药性。在本综述中，我们全面总结了GPX1多态性与癌症风险之间存在争议的关联，并进一步探讨了GPX1异常表达与肿瘤发生之间的关系。需要进一步研究来阐明GPX1作为各种恶性肿瘤潜在预后生物标志物和新型治疗靶点的临床意义。
