Background: Non-small cell lung cancer (NSCLC) mainly includes lung squamous cell carcinoma and lung adenocarcinoma, and its extremely high morbidity and mortality are the main causes of poor prognosis in NSCLC patients. Therefore, it is particularly important to study the mechanisms associated with tumor proliferation and metastasis and explore new molecular targets of NSCLC. Studies have shown that Guanosine monophosphate synthase (GMPS) may serve as a potential drug target, but its biological function and molecular mechanism in NSCLC are still unknown. Therefore, it is urgently needed to investigate the molecular mechanisms of GMPS.

Methods: We first analyzed 30 cases of lung adenocarcinoma, lung squamous carcinoma and adjacent tissues; Then, lentiviral technology was used to construct overexpressed or knocked out cell lines to verify the function of GMPS. Then, RNA sequencing and Western blot experiments were carried out in animal experiments to explore the mechanism of GMPS. Our experimental results suggest that GMPS plays an important role in the progression of NSCLC.

Results: We found that GMPS was highly expressed in lung adenocarcinoma and lung squamous cell carcinoma tissues, and was associated with poor prognosis of patients. Down-regulation of GMPS inhibits tumor progression. And GMPS promotes lung cancer cell migration through the SERPINB2-uPA axis, and DNMT1 is an intermediate factor in GMPS regulating SERPINB2 expression. Our experimental results show that GMPS expression is associated with lung cancer invasion and migration.

Conclusions: Our findings revealed the correlation between GMPS and the prognosis of NSCLC at the tissue level. Secondly, GMPS can promote the progression of NSCLC. The molecular mechanism of GMPS affecting the metastasis of lung cancer cells was elucidated. These findings highlight the important role of GMPS in NSCLC, so as to provide new insights for the identification of new targets and lay a theoretical foundation for the clinical application of GMPS.

Keywords: DNMT1; GMPS; Migration; Non-small cell lung cancer; SERPINB2.

© 2025. The Author(s).

背景: 非小细胞肺癌（NSCLC）主要包括肺鳞状细胞癌和肺腺癌，其极高的发病率和死亡率是导致 NSCLC 患者预后不良的主要原因。因此，研究与肿瘤增殖和转移相关的机制并探索新的分子靶点尤为重要。研究表明，鸟苷酸单磷酸合成酶（GMPS）可能作为潜在的药物靶点，但其在 NSCLC 中的生物学功能和分子机制仍不清楚。因此，迫切需要调查 GMPS 的分子机制。

方法: 我们首先分析了 30 例肺腺癌、肺鳞状细胞癌及邻近组织；然后使用 lentiviral 技术构建过表达或敲除的细胞系，验证 GMPS 功能。接着，在动物实验中进行 RNA 测序和 Western blot 实验以探索 GMPS 的机制。我们的实验结果表明 GMPS 在 NSCLC 进展中发挥重要作用。

结果: 我们发现 GMPS 在肺腺癌和肺鳞状细胞癌组织中高表达，并且与患者的不良预后相关。下调 GMPS 可抑制肿瘤进展。此外，GMPS 通过 SERPINB2-uPA 轴促进肺癌细胞迁移，DNMT1 是 GMPS 调节 SERPINB2 表达的中间因子。我们的实验结果表明 GMPS 的表达与肺癌侵袭和迁移有关。

结论: 我们的研究揭示了 GMPS 与 NSCLC 组织水平预后的相关性。其次，GMPS 可以促进 NSCLC 进展。阐明了 GMPS 影响肺癌细胞转移的分子机制。这些发现突显了 GMPS 在 NSCLC 中的重要作用，从而为识别新的靶点提供新见解，并为临床应用 GMPS 奠定了理论基础。

关键词: DNMT1；GMPS；迁移；非小细胞肺癌；SERPINB2.