Wang QingShui, Li ShengZhao, Xu YiNing, Chen Yuluo, Xu Chao, He QiuYan, Ye Yan, Huang YiMin, Wu Yue, Guo KeJia, Wei YaJuan, Huang Yide, Liu Yan, Lin Qing, Wang Shanshan, Li Feng, Huang Minghan, Xue FangQin, Lin Yao
The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, College of Integrative Medicine, Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China.
College of Life science, Fujian Normal University, Fuzhou, Fujian, China.
World J Surg Oncol. 2025 Jul 9;23(1):270. doi: 10.1186/s12957-025-03922-y.
Gastric cancer remains a leading cause of cancer-related mortality worldwide, characterized by poor prognosis due to its aggressive nature and high metastatic potential. While the E2-conjugating enzyme UBE2I (UBC9), essential for SUMOylation, has been implicated in various cancers, its precise role in gastric cancer remains poorly understood. In the study, we demonstrate significant UBC9 overexpression in gastric cancer tissues, which correlates with poor clinical outcomes. Functional analyses revealed that UBC9 knockdown significantly suppressed gastric cancer cell proliferation, migration, and invasion in vitro and in vivo, whereas UBC9 overexpression enhanced these malignant phenotypes. Through integrated transcriptomic and proteomic analyses, we identified ATF2 (Activating Transcription Factor 2) as a crucial downstream effector of UBC9-mediated oncogenic signaling. The mechanistic relationship between these factors was confirmed as ATF2 knockdown substantially attenuated the oncogenic effects of UBC9 overexpression. This newly identified UBC9-ATF2 regulatory axis promotes gastric cancer progression by enhancing cellular proliferation and metastatic potential. Our findings establish UBC9 and ATF2 as promising prognostic biomarkers and potential therapeutic targets, suggesting that intervention in the UBC9-ATF2 axis may provide novel therapeutic strategies for inhibiting gastric cancer progression and improving patient outcomes.
胃癌仍然是全球癌症相关死亡的主要原因，其侵袭性和高转移潜力导致预后不良。虽然E2结合酶UBE2I（UBC9）是SUMO化所必需的，已被证明与多种癌症有关，但其在胃癌中的具体作用仍知之甚少。在本研究中，我们证实在胃癌组织中UBC9显著过表达，这与不良临床结果相关。功能分析表明，敲低UBC9在体外和体内均显著抑制胃癌细胞的增殖、迁移和侵袭，而过表达UBC9则增强了这些恶性表型。通过整合转录组学和蛋白质组学分析，我们确定激活转录因子2（ATF2）是UBC9介导的致癌信号的关键下游效应因子。这些因子之间的机制关系得到证实，因为敲低ATF2可显著减弱UBC9过表达的致癌作用。这个新发现的UBC9-ATF2调控轴通过增强细胞增殖和转移潜力促进胃癌进展。我们的研究结果将UBC9和ATF2确立为有前景的预后生物标志物和潜在治疗靶点，表明干预UBC9-ATF2轴可能为抑制胃癌进展和改善患者预后提供新的治疗策略。
