Tan Hongpei, Liu Jiahao, Li Yanan, Mi Ze, Liu Baiying, Rong Pengfei
Department of Radiology, Third Xiangya Hospital, Central South University, Changsha, 410000, China.
Department of Gastrointestinal Surgery, Third Xiangya Hospital, Central South University, Changsha, China.
Cancer Cell Int. 2024 Apr 3;24(1):124. doi: 10.1186/s12935-024-03318-0.
Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent renal cancers, and the molecular mechanisms underlying its progression are still not fully understood. The expression of CCDC25, a notably underexpressed gene in many tumors, has been understudied in ccRCC. This research aims to explore the role of CCDC25 in ccRCC's clinical outcomes and uncover the molecular pathways influenced by it.
A multi-tiered approach was adopted involving bioinformatic analysis, tissue sample evaluation, in vitro and in vivo experiments. CCDC25 expression levels in tumor vs. normal tissues were quantified using Western blot and immunofluorescence studies. Cell proliferation and migration were analyzed using CCK8, EDU, Transwell assays, and wound healing assays. RNA sequencing was performed to elucidate the molecular pathways affected, followed by detailed protein-protein interaction studies and mouse xenograft models.
CCDC25 was predominantly underexpressed in ccRCC tumors and associated with advanced clinical stages and poor prognosis. Overexpression of CCDC25 in renal cancer cell lines resulted in reduced proliferation and migration. RNA sequencing revealed significant alterations in the Hippo pathway. Overexpression of CCDC25 inhibited the expression of downstream Hippo pathway proteins ITGA3 and CCND1 and promoted YAP phosphorylation. Mechanistic studies showed that CCDC25 interacts with YAP and influences YAP phosphorylation through LATS1. In vivo, CCDC25 overexpression inhibited tumor growth and promoted apoptosis.
CCDC25 acts as a potential tumor suppressor in ccRCC by inhibiting cell proliferation and migration, potentially through regulating the Hippo signaling pathway. These findings highlight the potential of CCDC25 as a therapeutic target in ccRCC treatment.
透明细胞肾细胞癌（ccRCC）是最常见的肾癌之一，其进展的分子机制仍未完全阐明。CCDC25在许多肿瘤中显著低表达，在ccRCC中的研究较少。本研究旨在探讨CCDC25在ccRCC临床结局中的作用，并揭示其影响的分子途径。
采用多层次方法，包括生物信息学分析、组织样本评估、体外和体内实验。使用蛋白质免疫印迹和免疫荧光研究定量肿瘤组织与正常组织中CCDC25的表达水平。使用CCK8、EDU、Transwell实验和伤口愈合实验分析细胞增殖和迁移。进行RNA测序以阐明受影响的分子途径，随后进行详细的蛋白质-蛋白质相互作用研究和小鼠异种移植模型。
CCDC25在ccRCC肿瘤中主要低表达，与晚期临床分期和不良预后相关。在肾癌细胞系中过表达CCDC25导致增殖和迁移减少。RNA测序显示Hippo通路有显著改变。CCDC25过表达抑制Hippo通路下游蛋白ITGA3和CCND1的表达，并促进YAP磷酸化。机制研究表明，CCDC25与YAP相互作用，并通过LATS1影响YAP磷酸化。在体内，CCDC25过表达抑制肿瘤生长并促进细胞凋亡。
CCDC25可能通过调节Hippo信号通路抑制细胞增殖和迁移，从而在ccRCC中发挥潜在的肿瘤抑制作用。这些发现突出了CCDC25作为ccRCC治疗靶点的潜力。
