各种研究表明，昼夜节律与肝细胞癌（HCC）的发生和发展有关。本研究的目的是研究昼夜节律基因在HCC中的特征、预后意义和靶向价值。通过生物信息学分析，研究了癌基因组图谱肝细胞癌（TCGA-LIHC）数据库中昼夜节律基因的表达特征和预后意义，并在一组本地HCC中运用免疫组织化学、Western blotting 和实时定量PCR (RT-qPCR) 进一步探究了强有力的标志基因Casein Kinase 1 Delta（CSNK1D）的表达特征。通过细胞计数试剂盒-8（CCK8）、流式细胞术、克隆实验、Transwell实验和异位移植实验评估了CSNK1D对HCC细胞相应表型的影响。此外，通过多重分子实验验证了CSNK1D在Wnt/β-catenin信号通路中的潜在机制。 昼夜节律基因的异常表达与HCC患者的恶性临床病理特征有关。通过Cox回归和最小绝对值收缩和选择算子（LASSO）分析，开发了基于10种昼夜节律基因的标志，具有显著的预后意义。其中，显著升高的CSNK1D在本地HCC队列中被选为进一步研究的对象。沉默或过表达CSNK1D分别显著降低或增加HCC细胞的增殖、侵袭、索拉非尼抗药性、异位移植发展和上皮-间质转化（EMT）。机械上，CSNK1D通过与分叉不良分割蛋白3（DVL3）相互作用来激活Wnt/β-catenin信号通路，从而加剧HCC细胞的侵袭性。 发现昼夜节律基因CSNK1D通过促进Wnt/β-catenin通路参与了HCC的进展，提示它可能是HCC的潜在治疗靶点。© 2022. 作者（们）。

A variety of studies have connected circadian rhythm to the initiation and progression of hepatocellular carcinoma (HCC). The purpose of this study was to figure out about the circadian genes' profile characteristics, prognostic significance, and targeted values in HCC.The expression profiles and prognostic significance of circadian genes in the cancer genome atlas liver hepatocellular carcinoma (TCGA-LIHC) database were investigated using bioinformatics analysis. The expression features of Casein Kinase 1 Delta (CSNK1D), a robust signature gene, was further detected by immunohistochemistry, western blotting and Real-time quantitative PCR (RT-qPCR) in a local HCC cohort. The effect of CSNK1D on corresponding phenotypes of HCC cells was evaluated using Cell Counting Kit-8 (CCK8), flowcytometry, clone assay, Transwell assay, and xenograft assay. In addition, the underlying mechanisms of CSNK1D in the Wnt/β-catenin signaling were validated by multiple molecular experiments.Abnormal expression of the Circadian genome was associated with the malignant clinicopathological characteristics of HCC patients. A 10 circadian gene-based signature with substantial prognostic significance was developed using Cox regression and least absolute shrinkage and selection operator (LASSO) analysis. Of them, CSNK1D, significantly elevated in a local HCC cohort, was chosen for further investigation. Silencing or overexpression of CSNK1D significantly reduced or increased proliferation, invasion, sorafenib resistance, xenograft development, and epithelial-mesenchymal transformation (EMT) of HCC cells, respectively. Mechanically, CSNK1D exacerbated the aggressiveness of HCC cells by activating Wnt/β-catenin signaling through interacting with Dishevelled Segment Polarity Protein 3 (DVL3).The Circadian gene CSNK1D was found to contribute to HCC progression by boosting the Wnt/β-catenin pathway, hinting that it could be a prospective therapeutic target for HCC.© 2022. The Author(s).