Jiang Hao, Tang Jingyuan, Cao Zhijun, Qiu Feng, Chai Zhuodong, Qi Jiaqian, Zhou Feng, Huang Yuhua
Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
Department of Urology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
J Cell Mol Med. 2025 Aug;29(15):e70773. doi: 10.1111/jcmm.70773.
Centromere-associated protein E (CENPE) has been identified as overexpressed in multiple cancers and exerts a tumour promotion function by affecting chromosome misalignment and mitosis. However, the expression pattern, biological roles, and underlying molecular mechanism of CENPE in clear cell renal cell carcinoma (ccRCC) progression have not been fully elucidated. In the present study, the expression levels of CENPE in ccRCC and paracancerous specimens were measured using the public RNA sequencing data and validated in a cohort of ccRCC samples from our centre. We found that CENPE was significantly over-expressed in ccRCC tissues and promoted proliferative and metastatic abilities of ccRCC cells and xenografts through regulating the epithelial-mesenchymal transition (EMT) process. Furthermore, bioinformatic analysis and ChIP assay indicated that the transcription factor CREB1 bound to the promoter region of CENPE and activated its transcription in ccRCC cells. Taken together, our findings demonstrated that the CREB1-CENPE axis was responsible for stimulating the in vitro and in vivo progression of ccRCC, serving as a promising therapeutic target for ccRCC.
着丝粒相关蛋白E（CENPE）已被确定在多种癌症中过表达，并通过影响染色体错配和有丝分裂发挥肿瘤促进作用。然而，CENPE在透明细胞肾细胞癌（ccRCC）进展中的表达模式、生物学作用及潜在分子机制尚未完全阐明。在本研究中，利用公开的RNA测序数据测定了CENPE在ccRCC及癌旁组织中的表达水平，并在我们中心的一组ccRCC样本中进行了验证。我们发现，CENPE在ccRCC组织中显著过表达，并通过调节上皮-间质转化（EMT）过程促进ccRCC细胞和异种移植瘤的增殖及转移能力。此外，生物信息学分析和染色质免疫沉淀试验表明，转录因子CREB1与CENPE的启动子区域结合并激活其在ccRCC细胞中的转录。综上所述，我们的研究结果表明，CREB1-CENPE轴负责刺激ccRCC的体外和体内进展，有望成为ccRCC的治疗靶点。
