Guo Linfa, Zhao Yiqiao, Bai Xiaojie, Wang Xiaolong, Tuoheti Kuerban, Cao Yuanfei, Zuo Yingtong, Zhang Xinhua, Liu Tongzu
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
J Cell Physiol. 2025 Jan;240(1):e31501. doi: 10.1002/jcp.31501. Epub 2024 Dec 16.
Bladder cancer (BLCA) is the tenth most common cancer worldwide, characterized by its high recurrence and progression rates. Thus, identifying prognostic biomarkers and understanding its underlying mechanisms are imperative to enhance patient outcomes. In this study, we aimed to investigate the prognostic significance, expression, functional activity, and underlying mechanisms of RRM2 in BLCA. RRM2 expression and its association with pathological grading and survival were investigated in samples from TCGA dataset and BLCA tissue microarray. CCK8 assays, colony formation assays, wound healing, and transwell assays were performed to assess the role of RRM2 in BLCA cell proliferation and migration. Western blot was employed to investigate alterations in markers associated with epithelial-to-mesenchymal transition (EMT), apoptosis, and cell cycle regulation. Gene set enrichment analysis was performed to investigate the biological processes associated with RRM2, which were subsequently validated. The expression of RRM2 was significantly elevated in both BLCA tissues and cells. Our results also indicated a positive correlation between RRM2 expression and high tumor stage, high tumor grade, and poor survival. Knockdown of RRM2 inhibited cell proliferation and migration of BLCA. RRM2 knockdown significantly induced apoptosis and arrested the cell cycle at the G0/G1 phase. Opposite results were observed in the RRM2 overexpression cells. Additionally, our study demonstrates that RRM2 promotes BLCA progression by activating the PI3K/AKT/mTOR pathway. RRM2 is remarkably correlated with poor prognosis in BLCA and facilitate its progression via PI3K/AKT/mTOR pathway. It is suggested that RRM2 might become an effective prognostic biomarker and potential therapeutic target for BLCA.
膀胱癌（BLCA）是全球第十大常见癌症，其特点是复发率和进展率高。因此，识别预后生物标志物并了解其潜在机制对于改善患者预后至关重要。在本研究中，我们旨在探讨RRM2在BLCA中的预后意义、表达、功能活性及潜在机制。在来自TCGA数据集和BLCA组织芯片的样本中研究了RRM2表达及其与病理分级和生存的相关性。进行CCK8检测、集落形成检测、伤口愈合检测和Transwell检测以评估RRM2在BLCA细胞增殖和迁移中的作用。采用蛋白质免疫印迹法研究与上皮-间质转化（EMT）、凋亡和细胞周期调控相关标志物的变化。进行基因集富集分析以研究与RRM2相关的生物学过程，随后进行验证。RRM2在BLCA组织和细胞中的表达均显著升高。我们的结果还表明RRM2表达与高肿瘤分期、高肿瘤分级和不良生存呈正相关。敲低RRM2可抑制BLCA细胞的增殖和迁移。敲低RRM2可显著诱导凋亡并使细胞周期停滞在G0/G1期。在RRM2过表达细胞中观察到相反的结果。此外，我们的研究表明RRM2通过激活PI3K/AKT/mTOR通路促进BLCA进展。RRM2与BLCA的不良预后显著相关，并通过PI3K/AKT/mTOR通路促进其进展。提示RRM2可能成为BLCA有效的预后生物标志物和潜在的治疗靶点。
