Zhao Jie, Dai Juanjuan, Zhou Ning, Liu Dongqin, Wang Dandan, Miao Shuang, Liang Chao, An Di, Jiang Jiatong, Gong Kaikai, Wu Yan
Department of Oncology, Binzhou Medical University Hospital, Binzhou, People's Republic of China.
Medical Research Center, Binzhou Medical University Hospital, Binzhou, 256603, People's Republic of China.
Genes Genomics. 2025 Feb 20. doi: 10.1007/s13258-025-01623-0.
Non-small-cell-lung-cancer (NSCLC) is a prevalent lung malignancy among humans. UBE2C is a critical component of the ubiquitin-proteasome system, and its expression level is significantly associated with cancer development and cell proliferation. Nevertheless, the mechanisms of UBE2C in NSCLC remain unclear.
We aimed to investigate the role of MMP9 in UBE2C-overexpressed NSCLC progression.
The GEPIA database and Kaplan-Meier curves were used to determine UBE2C expression in human tumors and survival in NSCLC. CCK8, colony formation, and Transwell assays were employed to assess the function of UBE2C in vitro. Western blotting, immunofluorescence assay, and RT-qPCR were utilized to determine protein and mRNA expression levels. CHX chase and co-immunoprecipitation assays were used to elucidate the regulatory mechanism.
This research proved that UBE2C expression was related to patient overall survival, cell proliferation and migration. Furthermore, overexpressed UBE2C could promote the protein stability of Matrix metalloproteinase-9 (MMP9) to upregulate its protein level in NSCLC cells. Meanwhile, UBE2C upregulation promoted lung carcinoma progression by modulating MMP9 expression.
Our findings indicate that UBE2C may be a therapeutic and prognostic target for lung carcinoma.
非小细胞肺癌（NSCLC）是人类中一种常见的肺部恶性肿瘤。泛素结合酶E2C（UBE2C）是泛素-蛋白酶体系统的关键组成部分，其表达水平与癌症发展和细胞增殖显著相关。然而，UBE2C在NSCLC中的作用机制仍不清楚。
我们旨在研究基质金属蛋白酶9（MMP9）在UBE2C过表达的NSCLC进展中的作用。
利用GEPIA数据库和Kaplan-Meier曲线确定UBE2C在人类肿瘤中的表达以及NSCLC患者的生存率。采用CCK8、集落形成和Transwell实验在体外评估UBE2C的功能。利用蛋白质免疫印迹法、免疫荧光实验和RT-qPCR确定蛋白质和mRNA表达水平。采用CHX追踪实验和免疫共沉淀实验阐明调控机制。
本研究证明UBE2C表达与患者总生存期、细胞增殖和迁移有关。此外，UBE2C过表达可促进基质金属蛋白酶9（MMP9）的蛋白质稳定性，从而上调NSCLC细胞中MMP9的蛋白质水平。同时，UBE2C上调通过调节MMP9表达促进肺癌进展。
我们的研究结果表明，UBE2C可能是肺癌治疗和预后的一个靶点。
