Zhou Jie, Wang Yu-Hui, Li Yong-Le, Xie Xiao-Mei, Jiang Zhou, Zhuo Xin, Shan Xu-Dong, Cheng Shu-Tin, Jiang Li-He
School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, Guangxi, People's Republic of China.
Medical College, Guangxi University, Nanning, Guangxi, People's Republic of China.
J Cancer Res Clin Oncol. 2025 Sep 27;151(10):269. doi: 10.1007/s00432-025-06321-8.
Some studies have shown that circadian rhythms are associated with the development and progression of hepatocellular carcinoma (HCC). In this study, we aimed to elucidate the characterization, prognostic significance and targeting value of circadian rhythm gene CSNK1E in HCC.
In this study, relevant datasets were downloaded from TCGA and GEO databases and analyzed for differences respectively. The key modules of the prognosis-related gene set were identified using WGCNA, and the intersection of the key module genes with 48 circadian rhythm genes was taken and analyzed in single-cell data. The identification of key circadian rhythm genes in HCC aimed to analyze the expression, prognostic significance, and clinically relevant features of CSNK1E in cancer. The expression characteristics of CSNK1E were further examined by immunohistochemistry, western blotting (WB), and Real-time quantitative PCR (qRT-PCR). The effects of CSNK1E on the phenotypes of HCC cells were evaluated using Cell Counting Kit-8 (CCK8), flow cytometry, Transwell assay and Wound healing assay. Furthermore, transcriptomic analysis identified HIPPO signaling pathway as a potential pathway involving CSNK1E. The functional role of CSNK1E in HIPPO signaling was subsequently validated through western blotting (WB) and quantitative real-time PCR (qRT-PCR) assays.
We constructed a prognostic model of key circadian rhythm-related genes (CSNK1E, CSNK1D, CSNK2A1, and CSNK2B) to predict the prognosis and survival of HCC patients. The high-risk group had a worse prognosis compared to the low-risk group, which was confirmed by ROC curves and survival curves. CSNK1E expression levels were significantly associated with clinicopathological features and identified as a robust and independent prognostic biomarker in HCC. Higher CSNK1E expression levels were associated with poorer overall survival in various clinical subgroups. The cell experiment showed that CSNK1E knockdown suppressed cell proliferation, migration, and invasion while promoting apoptosis; its overexpression produced opposite effects. Moreover, CSNK1E may mediate HCC cell proliferation through Hippo signaling pathway.
The finding that the circadian gene CSNK1E contributes to HCC progression through activation of HIPPO signaling pathway suggests that it may be a promising therapeutic target for HCC.
一些研究表明昼夜节律与肝细胞癌（HCC）的发生发展相关。在本研究中，我们旨在阐明昼夜节律基因CSNK1E在HCC中的特征、预后意义及靶向价值。
本研究从TCGA和GEO数据库下载相关数据集并分别进行差异分析。使用WGCNA确定预后相关基因集的关键模块，取关键模块基因与48个昼夜节律基因的交集并在单细胞数据中进行分析。在HCC中鉴定关键昼夜节律基因旨在分析CSNK1E在癌症中的表达、预后意义及临床相关特征。通过免疫组织化学、蛋白质免疫印迹法（WB）和实时定量聚合酶链反应（qRT-PCR）进一步检测CSNK1E的表达特征。使用细胞计数试剂盒-8（CCK8）、流式细胞术、Transwell实验和伤口愈合实验评估CSNK1E对HCC细胞表型的影响。此外，转录组分析确定HIPPO信号通路是涉及CSNK1E的潜在通路。随后通过蛋白质免疫印迹法（WB）和定量实时聚合酶链反应（qRT-PCR）实验验证CSNK1E在HIPPO信号传导中的功能作用。
我们构建了关键昼夜节律相关基因（CSNK1E、CSNK1D、CSNK2A1和CSNK2B）的预后模型以预测HCC患者的预后和生存情况。与低风险组相比，高风险组预后更差，这通过ROC曲线和生存曲线得到证实。CSNK1E表达水平与临床病理特征显著相关，并被确定为HCC中一个可靠且独立的预后生物标志物。在各个临床亚组中，较高的CSNK1E表达水平与较差的总生存期相关。细胞实验表明，敲低CSNK1E可抑制细胞增殖、迁移和侵袭，同时促进细胞凋亡；其过表达则产生相反的效果。此外，CSNK1E可能通过Hippo信号通路介导HCC细胞增殖。
昼夜节律基因CSNK1E通过激活Hippo信号通路促进HCC进展这一发现表明，它可能是HCC一个有前景的治疗靶点。
