{"title":"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。","authors":"Mengqi Zhu, Jianping Zhang, Saiyan Bian, Xue Zhang, Yiping Shen, Zhiyu Ni, Shiyu Xu, Chun Cheng, Wenjie Zheng","doi":"10.1186/s12575-022-00183-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"24 1","pages":"21"},"PeriodicalIF":3.7000,"publicationDate":"2022-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9717411/pdf/","citationCount":"4","resultStr":"{\"title\":\"Circadian gene CSNK1D promoted the progression of hepatocellular carcinoma by activating Wnt/β-catenin pathway via stabilizing Dishevelled Segment Polarity Protein 3.\",\"authors\":\"Mengqi Zhu, Jianping Zhang, Saiyan Bian, Xue Zhang, Yiping Shen, Zhiyu Ni, Shiyu Xu, Chun Cheng, Wenjie Zheng\",\"doi\":\"10.1186/s12575-022-00183-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":8960,\"journal\":{\"name\":\"Biological Procedures Online\",\"volume\":\"24 1\",\"pages\":\"21\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2022-12-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9717411/pdf/\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biological Procedures Online\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s12575-022-00183-x\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biological Procedures Online","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s12575-022-00183-x","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Circadian gene CSNK1D promoted the progression of hepatocellular carcinoma by activating Wnt/β-catenin pathway via stabilizing Dishevelled Segment Polarity Protein 3.
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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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:
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Biological Procedures Online places emphasis on multidisciplinary approaches that integrate methodologies from medicine, biology, chemistry, imaging, engineering, bioinformatics, computer science, and systems analysis.
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