Circadian gene CSNK1D promoted the progression of hepatocellular carcinoma by activating Wnt/β-catenin pathway via stabilizing Dishevelled Segment Polarity Protein 3.

IF 3.7 3区生物学 Q1 BIOCHEMICAL RESEARCH METHODS Biological Procedures Online Pub Date : 2022-12-02 DOI:10.1186/s12575-022-00183-x

Mengqi Zhu, Jianping Zhang, Saiyan Bian, Xue Zhang, Yiping Shen, Zhiyu Ni, Shiyu Xu, Chun Cheng, Wenjie Zheng

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引用次数: 4

Abstract

Purpose: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

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昼夜节律基因CSNK1D通过稳定散乱片段极性蛋白3激活Wnt/β-catenin通路，促进肝癌的进展。

目的:各种研究已经将昼夜节律与肝细胞癌(HCC)的发生和发展联系起来。本研究的目的是了解HCC中昼夜节律基因的谱特征、预后意义和靶向价值。方法:应用生物信息学方法研究肝癌基因组图谱(TCGA-LIHC)数据库中昼夜节律基因的表达谱及其预后意义。应用免疫组织化学、western blotting和实时荧光定量PCR (RT-qPCR)技术进一步检测了酪蛋白激酶1 δ (Casein Kinase 1 Delta, CSNK1D)的表达特征。采用细胞计数试剂盒-8 (CCK8)、流式细胞术、克隆实验、Transwell实验和异种移植实验评估CSNK1D对HCC细胞相应表型的影响。此外，通过多个分子实验验证了CSNK1D在Wnt/β-catenin信号传导中的潜在机制。结果:昼夜节律基因组的异常表达与HCC患者的恶性临床病理特征有关。使用Cox回归和最小绝对收缩和选择算子(LASSO)分析，开发了具有重大预后意义的10个昼夜节律基因特征。其中，CSNK1D在当地HCC队列中显著升高，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、索拉非尼耐药、异种移植物发育和上皮-间质转化(EMT)。机制上，CSNK1D通过与凌乱片段极性蛋白3 (DVL3)相互作用激活Wnt/β-catenin信号，从而加剧了HCC细胞的侵袭性。结论:研究发现昼夜节律基因CSNK1D通过促进Wnt/β-catenin通路促进HCC进展，提示其可能是HCC的前瞻性治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biological Procedures Online 生物-生化研究方法

CiteScore

10.50

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： iological Procedures Online publishes articles that improve access to techniques and methods in the medical and biological sciences. We are also interested in short but important research discoveries, such as new animal disease models. Topics of interest include, but are not limited to: Reports of new research techniques and applications of existing techniques Technical analyses of research techniques and published reports Validity analyses of research methods and approaches to judging the validity of research reports Application of common research methods Reviews of existing techniques Novel/important product information Biological Procedures Online places emphasis on multidisciplinary approaches that integrate methodologies from medicine, biology, chemistry, imaging, engineering, bioinformatics, computer science, and systems analysis.