Casein kinase 1 family member CSNK1E can regulate proliferation and migration in hepatocellular carcinoma.

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.