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

Sep 24, 2026

Purpose: Clarify the characterization, prognostic relevance, and therapeutic targeting potential of circadian rhythm gene CSNK1E in hepatocellular carcinoma (HCC). Methods: Download and analyze datasets from TCGA and GEO, identify prognosis-related gene modules using WGCNA, intersect key modules with circadian genes, and validate findings with single-cell analyses. Assess expression by immunohistochemistry, western blotting, and qRT-PCR; evaluate cellular phenotypes using CCK8, flow cytometry, Transwell, and wound-healing assays. Results: Build a prognostic model based on circadian genes, showing CSNK1E as an independent biomarker; functional assays indicate CSNK1E knockdown suppresses proliferation, migration, invasion, and promotes apoptosis, with opposite effects upon overexpression. Transcriptomics implicates the Hippo signaling pathway. Conclusions: CSNK1E promotes HCC progression via HIPPO signaling and may represent a promising therapeutic target.

LanguageEnglish

CategoryResearch & Report

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Reading Time50 min

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Abstract

Purpose

Methods

Results

Conclusions

Journal of Cancer Research and Clinical Oncology (2025) 151:269 [https://doi.org/10.1007/s00432-025-06321-8](https://doi.org/10.1007/s00432-025-06321-8) RESEARCH Casein kinase 1 family member CSNK1E can regulate proliferation and migration in hepatocellular carcinoma Jie Zhou1,2 · Yu-Hui Wang3 · Yong-Le Li1 · Xiao-Mei Xie1 · Zhou Jiang3,7 · Xin Zhuo3,6 · Xu-dong Shan5 · Shu-Tin Cheng3,7 · Li-He Jiang1,2,3,4 Received: 22 April 2025 / Accepted: 10 September 2025 / Published online: 27 September 2025 © The Author(s) 2025 Abstract 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 ofthe 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. Keywords CSNK1E · HCC · Bioinformatics · HIPPO signaling pathway Abbreviations HCC TCGA-LIHC GEO Hepatocellular carcinoma The cancer genome atlas liver hepatocellular carcinoma Gene expression omnibus CSNK1EIHC WB WGCNA Casein kinase 1 epsilon Immunohistochemistry Western blotting Weighted gene co-expression network analysis Jie Zhou and Yu-Hui Wang have been contributed equally to this work. Extended author information available on the last page of the article qRT-PCR Quantitative real-time PCR GS Gene significance MS Module significance CCK8 Cell counting kit-8 CK1 Casein kinase 1 ROC Receiver operating characteristic GSE Gene expression omnibus series NCBI National center for biotechnology information GEO Gene expression omnibus GSEA Gene set enrichment analysis FDR False discovery rate DMEM Durbek’s modified eagle medium FBS Fetal bovine serum PBS Phosphate buffer siRNA Small interfering RNA SD Standard deviation DAB Diaminobenzidine DAPI 4′,6-diamidino-2′-phenylindole

FAQs

What is the main purpose of studying CSNK1E in hepatocellular carcinoma?

The study aims to characterize CSNK1E, determine its prognostic significance in HCC, and evaluate its potential as a therapeutic target.

How were datasets and key genes analyzed in the study?

Relevant datasets were downloaded from TCGA and GEO, prognosis-related gene modules were identified using WGCNA, key module genes were intersected with circadian rhythm genes, and single-cell data were used for further analysis.

What experimental evidence supports CSNK1E’s role in HCC cell behavior?

CSNK1E knockdown reduced proliferation, migration, and invasion while promoting apoptosis; CSNK1E overexpression produced opposite effects, assessed with CCK8, flow cytometry, Transwell, and wound-healing assays.

Sep 24, 2026

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