GMPS inhibits the proliferation and migration of non-small cell lung cancer via the regulation of the DNMT 1/SERPINB2 axis.

IF 4.8 2区医学 Q2 CELL BIOLOGY

Cellular Oncology Pub Date : 2025-08-01 Epub Date: 2025-06-11 DOI:10.1007/s13402-025-01078-1

Tingting Guo, Lei Liu, Lingyan Zeng, Ying Yang, Tingting Song, Huachang Zhao, Zhixin Qiu

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引用次数: 0

Abstract

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.

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GMPS通过调控DNMT 1/SERPINB2轴抑制非小细胞肺癌的增殖和迁移。

背景：非小细胞肺癌（Non-small cell lung cancer， 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NSCLC患者预后不良的主要原因。因此，研究肿瘤增殖转移的相关机制，探索NSCLC新的分子靶点就显得尤为重要。研究表明，鸟苷单磷酸合成酶（Guanosine monophosphate synthase， GMPS）可能是一个潜在的药物靶点，但其在NSCLC中的生物学功能和分子机制尚不清楚。因此，迫切需要研究gmp的分子机制。方法：首先对30例肺腺癌、肺鳞癌及其邻近组织进行分析；然后，利用慢病毒技术构建过表达或敲除细胞系，验证GMPS的功能。然后在动物实验中进行RNA测序和Western blot实验，探讨GMPS的作用机制。我们的实验结果表明GMPS在NSCLC的进展中起着重要的作用。结果：我们发现GMPS在肺腺癌和肺鳞状细胞癌组织中高表达，并与患者预后不良相关。下调GMPS抑制肿瘤进展。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的表达与肺癌的侵袭和迁移有关。结论：我们的研究结果在组织水平上揭示了GMPS与非小细胞肺癌预后的相关性。其次，GMPS可以促进NSCLC的进展。阐明了GMPS影响肺癌细胞转移的分子机制。这些发现突出了GMPS在NSCLC中的重要作用，从而为新靶点的鉴定提供了新的见解，为GMPS的临床应用奠定了理论基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular Oncology ONCOLOGY-CELL BIOLOGY

CiteScore

10.30

自引率

1.50%

发文量

审稿时长

12 months

期刊介绍： The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.