Song Jie, Guo Wenying, Xu Hua, Gao Tao
Department of Cardiac surgery, Ningbo medical center Lihuili Hospital of Ningbo University, No.57, Xingning Road, Ningbo city 315041, Zhejiang Province, China.
Department of Digestive, Ningbo medical center Lihuili Hospital of Ningbo University, No.57, Xingning Road, Ningbo city 315041, Zhejiang Province, China.
Heliyon. 2024 Apr 24;10(9):e29904. doi: 10.1016/j.heliyon.2024.e29904. eCollection 2024 May 15.
The role of human cell division cycle 73 (CDC73) in human cancers has sparked controversy; however, its significance in oesophageal cancer remains elusive. This study aimed to elucidate CDC73 expression and its biological implications in human oesophageal cancer. Our findings unveiled a notable upregulation of CDC73 in both oesophageal cancer cell lines and tissues. Importantly, elevated CDC73 levels in patients with oesophageal cancer correlated with an unfavourable prognosis. Functional investigations revealed that CDC73 knockdown effectively curtailed the proliferation and growth of oesophageal cancer cells both and . Mechanistically, RRP15 emerged as a potential downstream target of CDC73 through a screening process involving identification of the top co-expressed genes, subsequent knockdown experiments, and observation of significant inhibition of cell proliferation, with RRP15 showing the most pronounced effect. This finding was further supported by the positive correlation observed between CDC73 and RRP15 in ESCA samples analysed using the ENCORI Pan-Cancer Analysis Platform. Notably, depletion of RRP15 in CDC73-overexpressing cells led to a shift from augmented to diminished tumour growth. Collectively, our findings underscore the pivotal role of CDC73 in oesophageal cancer through the modulation of RRP15 expression, suggesting CDC73 as a potential therapeutic target for treating oesophageal cancer.
人类细胞分裂周期73（CDC73）在人类癌症中的作用引发了争议；然而，其在食管癌中的意义仍不明确。本研究旨在阐明CDC73在人类食管癌中的表达及其生物学意义。我们的研究结果揭示了CDC73在食管癌细胞系和组织中均有显著上调。重要的是，食管癌患者中CDC73水平升高与不良预后相关。功能研究表明，敲低CDC73可有效抑制食管癌细胞的增殖和生长。从机制上讲，通过一个筛选过程，RRP15成为CDC73的潜在下游靶点，该过程包括识别共表达最高的基因、随后的敲低实验以及观察到细胞增殖受到显著抑制，其中RRP15的作用最为明显。使用ENCORI泛癌分析平台分析的ESCA样本中CDC73与RRP15之间的正相关进一步支持了这一发现。值得注意的是，在过表达CDC73的细胞中敲低RRP15导致肿瘤生长从增强转变为减弱。总体而言，我们的研究结果强调了CDC73通过调节RRP15表达在食管癌中的关键作用，表明CDC73作为治疗食管癌的潜在治疗靶点。
