Department of Urology, Hebei Medical University Third Hospital, Shijiazhuang, China.
Faculty of Health and Behavioural Sciences, The University of Queensland, Queensland, Australia.
J Cell Mol Med. 2024 Jun;28(11):e18473. doi: 10.1111/jcmm.18473.
Bladder cancer is one of the most prevalent cancers worldwide, and its morbidity and mortality rates have been increasing over the years. However, how RAC family small GTPase 3 (RAC3) affects the proliferation, migration and invasion of cisplatin-resistant bladder cancer cells remains unclear. Bioinformatics techniques were used to investigate the expression of RAC3 in bladder cancer tissues. Influences of RAC3 in the grade, stage, distant metastasis, and survival rate of bladder cancer were also examined. Analysis of the relationship between RAC3 expression and the immune microenvironment (TIME), genomic mutations, and stemness index. In normal bladder cancer cells (T24, 5637, and BIU-87) and cisplatin-resistant bladder cancer cells (BIU-87-DDP), the expression of RAC3 was detected separately with Western blotting. Plasmid transfection was used to overexpress or silence the expression of RAC3 in bladder cancer cells resistant to cisplatin (BIU-87-DDP). By adding activators and inhibitors, the activities of the JNK/MAPK signalling pathway were altered. Cell viability, invasion, and its level of apoptosis were measured in vitro using CCK-8, transwell, and flow cytometry. The bioinformatics analyses found RAC3 levels were elevated in bladder cancer tissues and were associated with a poor prognosis in bladder cancer. RAC3 in BIU-87-DDP cells expressed a higher level than normal bladder cancer cells. RAC3 overexpression promoted BIU-87-DDP proliferation. The growth of BIU-87-DDP cells slowed after the knockdown of RAC3, and RAC3 may have had an impact on the activation of the JNK/MAPK pathway.
膀胱癌是全球最常见的癌症之一,其发病率和死亡率近年来一直在上升。然而,RAC 家族小 GTP 酶 3(RAC3)如何影响顺铂耐药膀胱癌细胞的增殖、迁移和侵袭尚不清楚。本研究采用生物信息学技术分析 RAC3 在膀胱癌组织中的表达情况,探讨 RAC3 在膀胱癌分级、分期、远处转移和生存率中的影响。分析 RAC3 表达与肿瘤免疫微环境(TIME)、基因组突变和干性指数的关系。分别用 Western blot 检测正常膀胱癌细胞(T24、5637 和 BIU-87)和顺铂耐药膀胱癌细胞(BIU-87-DDP)中 RAC3 的表达。用质粒转染过表达或沉默顺铂耐药膀胱癌细胞(BIU-87-DDP)中 RAC3 的表达。通过添加激活剂和抑制剂改变 JNK/MAPK 信号通路的活性。用 CCK-8、Transwell 和流式细胞术检测细胞活力、侵袭和细胞凋亡水平。生物信息学分析发现 RAC3 在膀胱癌组织中表达升高,与膀胱癌预后不良相关。BIU-87-DDP 细胞中 RAC3 的表达水平高于正常膀胱癌细胞。RAC3 过表达促进 BIU-87-DDP 增殖。敲低 RAC3 后 BIU-87-DDP 细胞的生长速度减慢,RAC3 可能影响 JNK/MAPK 通路的激活。