Department of Thoracic Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Department of Thoracic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Physiol Genomics. 2023 May 1;55(5):213-221. doi: 10.1152/physiolgenomics.00001.2023. Epub 2023 Mar 20.
Current research has shown that inhibiting deoxythymidylate kinase (DTYMK) can significantly reduce development of lung cancer without liver kinase B1. However, its underlying regulatory mechanism is still unclear. We therefore aimed to investigate whether DTYMK inhibitors could suppress lung adenocarcinoma (LUAD) progression. In this study, human tissues, A549 cells, and xenograft tumors were used to explore the regulation and mechanism of DTYMK on LUAD cell proliferation and migration. Meanwhile, YMU1 (a DTYMK inhibitor) was applied to A549 cells and xenograft tumors to investigate its potential as a drug for LUAD. DTYMK was overexpressed in LUAD tissues and correlated with tumor stage. Knockdown of DTYMK suppressed cell viability, migration, and invasion. In addition, the activation of signal transducers and activators of transcription 3 (STAT3) was repressed upon DTYMK inhibition. YMU1 showed the same effect as DTYMK knockdown in vivo and in vitro. DTYMK plays an important role in progression of LUAD through the STAT3 signaling pathway. YMU1 may have the potential to inhibit the development of LUAD. DTYMK plays an important role in progression of LUAD through the STAT3 signaling pathway. YMU1 may serve as a novel drug to suppress the development of LUAD.
目前的研究表明，抑制脱氧胸苷酸激酶（DTYMK）可以在没有肝激酶 B1 的情况下显著减少肺癌的发展。然而，其潜在的调节机制尚不清楚。因此，我们旨在研究 DTYMK 抑制剂是否可以抑制肺腺癌（LUAD）的进展。在这项研究中，使用人类组织、A549 细胞和异种移植肿瘤来探索 DTYMK 对 LUAD 细胞增殖和迁移的调节和机制。同时，将 YMU1（一种 DTYMK 抑制剂）应用于 A549 细胞和异种移植肿瘤，以研究其作为 LUAD 药物的潜力。DTYMK 在 LUAD 组织中过度表达，并与肿瘤分期相关。敲低 DTYMK 抑制细胞活力、迁移和侵袭。此外，STAT3（信号转导和转录激活因子 3）的激活在 DTYMK 抑制时受到抑制。YMU1 在体内和体外均表现出与 DTYMK 敲低相同的效果。DTYMK 通过 STAT3 信号通路在 LUAD 的进展中起重要作用。YMU1 可能具有抑制 LUAD 发展的潜力。DTYMK 通过 STAT3 信号通路在 LUAD 的进展中起重要作用。YMU1 可能作为一种新型药物抑制 LUAD 的发展。
