REG3A, a prominent member of the human regenerating islet-derived (REG) lectin family, plays a pivotal and multifaceted role in immune defense, inflammation, and cancer biology. Primarily expressed in gastrointestinal epithelial cells, REG3A reinforces barrier integrity, orchestrates mucosal immune responses, and regulates host–microbiota interactions. It also functions as a potent non-enzymatic antioxidant, protecting tissues from oxidative stress. REG3A expression is tightly regulated by inflammatory stimuli and is robustly induced during immune activation, where it limits microbial invasion, dampens tissue injury, and promotes epithelial repair. Beyond its antimicrobial and immunomodulatory properties, REG3A contributes to the resolution of inflammation and the maintenance of tissue homeostasis. However, its role in cancer is highly context-dependent. In some tumor types, REG3A fosters malignant progression by enhancing cell survival, proliferation, and invasiveness. In others, it acts as a tumor suppressor, inhibiting growth and metastatic potential. These opposing effects are likely dictated by a combination of factors, including the tissue of origin, the composition and dynamics of the tumor microenvironment, and the stage of disease progression. Additionally, the secreted nature of REG3A implies both local and systemic effects, further modulated by organ-specific physiology. Experimental variability may also reflect differences in methodologies, analytical tools, and model systems used. This review synthesizes current knowledge on the pleiotropic functions of REG3A, emphasizing its roles in epithelial defense, immune regulation, redox homeostasis, and oncogenesis. A deeper understanding of REG3A’s pleiotropic effects could open up new therapeutic avenues in both inflammatory disorders and cancer.
REG3A是人类再生胰岛衍生（REG）凝集素家族的重要成员，在免疫防御、炎症反应和癌症生物学中发挥着关键且多方面的作用。该蛋白主要在胃肠道上皮细胞中表达，能够增强屏障完整性、协调黏膜免疫应答并调节宿主-微生物群相互作用。同时，REG3A作为一种强效的非酶类抗氧化剂，可保护组织免受氧化应激损伤。其表达受炎症刺激的严格调控，在免疫激活过程中被显著诱导，通过限制微生物入侵、减轻组织损伤并促进上皮修复发挥作用。除了抗菌和免疫调节特性外，REG3A还参与炎症消退和组织稳态的维持。然而，其在癌症中的作用具有高度情境依赖性：在某些肿瘤类型中，REG3A通过增强细胞存活、增殖和侵袭能力促进恶性进展；而在其他类型中则发挥抑癌作用，抑制肿瘤生长和转移潜能。这些相反效应可能受多种因素共同影响，包括组织来源、肿瘤微环境的组成与动态变化以及疾病进展阶段。此外，REG3A的分泌特性意味着其同时具有局部和全身效应，并进一步受到器官特异性生理调节。实验结果的差异也可能反映研究方法、分析工具和模型系统的不同。本文综述了当前对REG3A多效性功能的认识，重点阐述其在上皮防御、免疫调节、氧化还原稳态和肿瘤发生中的作用。深入理解REG3A的多效性效应，可能为炎症性疾病和癌症的治疗开辟新途径。
肿瘤(癌症)患者之家