Li Xiaojia, Wang Yu, Liu Yan, Meng Qingwei
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Medical Oncology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Eur J Med Res. 2025 Apr 29;30(1):343. doi: 10.1186/s40001-025-02581-9.
Despite recent progress in understanding lung adenocarcinoma (LUAD) and the emergence of new therapeutic strategies, LUAD continues to be one of the deadliest lung cancer types, with a five-year survival rate of under 5%. Opsin3 (OPN3), a member of the G protein-coupled receptor superfamily, has been linked to various cancer-related processes, including tumor progression and therapy resistance. However, its specific role in LUAD remains insufficiently investigated. This study aimed to explore OPN3's regulatory functions in LUAD and evaluate its potential as a therapeutic target. OPN3 expression in LUAD cells was assessed using quantitative PCR, Western blotting, and immunohistochemistry. The effects of OPN3 on cell migration and invasion were evaluated through wound healing and transwell assays. Additionally, the influence of OPN3 on cell cycle progression and signaling pathways in vivo-critical for cellular responses to external stimuli-was examined. Pathway enrichment analysis revealed significant disruption of genes associated with glutathione metabolism. Notably, a strong correlation between OPN3 expression and the regulation of Glutathione Peroxidase 3 (GPX3), a key enzyme in this metabolic pathway, was identified. Our results demonstrate that OPN3 is markedly overexpressed in LUAD tissues relative to normal lung tissues. Silencing OPN3 via siRNA significantly diminished the malignant features of LUAD cells, including proliferation, migration, and invasion. In contrast, OPN3 overexpression enhanced these malignant characteristics, indicating its involvement in tumor progression. Moreover, an inverse relationship between OPN3 expression and GPX3 levels was observed, suggesting that OPN3 may drive LUAD progression through the GPX3 pathway. This study offers new insights into the function of OPN3 in LUAD and suggests that targeting the OPN3-GPX3 axis could provide a promising therapeutic strategy for LUAD patients.
尽管在理解肺腺癌（LUAD）方面取得了最新进展，并且出现了新的治疗策略，但LUAD仍然是最致命的肺癌类型之一，五年生存率低于5%。视蛋白3（OPN3）是G蛋白偶联受体超家族的成员，与各种癌症相关过程有关，包括肿瘤进展和治疗抗性。然而，其在LUAD中的具体作用仍未得到充分研究。本研究旨在探索OPN3在LUAD中的调节功能，并评估其作为治疗靶点的潜力。使用定量PCR、蛋白质印迹和免疫组织化学评估LUAD细胞中OPN3的表达。通过伤口愈合和Transwell实验评估OPN3对细胞迁移和侵袭的影响。此外，还研究了OPN3对体内细胞周期进程和信号通路的影响，这些对于细胞对外部刺激的反应至关重要。通路富集分析揭示了与谷胱甘肽代谢相关基因的显著破坏。值得注意的是，确定了OPN3表达与该代谢途径中的关键酶谷胱甘肽过氧化物酶3（GPX3）的调节之间存在强相关性。我们的结果表明，相对于正常肺组织，OPN3在LUAD组织中明显过表达。通过小干扰RNA（siRNA）沉默OPN3可显著降低LUAD细胞的恶性特征，包括增殖、迁移和侵袭。相反，OPN3过表达增强了这些恶性特征，表明其参与肿瘤进展。此外，观察到OPN3表达与GPX3水平之间呈负相关，表明OPN3可能通过GPX3途径推动LUAD进展。本研究为OPN3在LUAD中的功能提供了新的见解，并表明靶向OPN3-GPX3轴可能为LUAD患者提供一种有前景的治疗策略。
