Reference - Detail
|Author||Chen C, Ge C, Liu Z, Li L, Zhao F, Tian H, Chen T, Li H, Yao M, Li J.|
|Title||ATF3 inhibits the tumorigenesis and progression of hepatocellular carcinoma cells via upregulation of CYR61 expression.|
|Journal||J Exp Clin Cancer Res|
BACKGROUND:Hepatocellular carcinoma (HCC) is one of the most common malignant cancers with a high incidence and high mortality in East Asia. Identifying biomarkers and clarifying the regulatory mechanisms of HCC are of great importance. Herein, we report the role and mechanism of activating transcription factor 3 (ATF3), a member of the ATF/cAMP-responsive element-binding protein family of transcription factors in HCC.
METHODS:ATF3 overexpression vector and shRNAs were transfected into HCC cancer cells to upregulate or downregulate ATF3 expression. In vitro and in vivo assays were performed to investigate the functional role of ATF3 in hepatocellular carcinoma. RNA-Seq was performed to screen the differentially expressed genes downstream of ATF3. The dual-luciferase reporter assay, chromatin immunoprecipitation (Ch-IP) analysis and functional rescue experiments were used to confirm the target gene regulated by ATF3. Tissue microarrays (TMAs) comprising 236 human primary HCC tissues were obtained and immunohistochemical staining were carried out to analyze the clinical significance of ATF3.
RESULTS:The results indicate that ATF3 significantly inhibited the proliferation and mobility of HCC cells both in vitro and in vivo. Cysteine-rich angiogenic inducer 61 (CYR61) is a key target for transcriptional regulation by ATF3. Both ATF3 and CYR61 were consistently downregulated in human HCC tissues, and their expression levels were significantly and positively correlated with each other.
CONCLUSIONS:Our findings indicate that ATF3 functions as a tumor suppressor in HCC through targeting and regulating CYR61.
|MeSH||Activating Transcription Factor 3 / genetics* Activating Transcription Factor 3 / metabolism Animals Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / metabolism Carcinoma, Hepatocellular / pathology* Cell Line, Tumor Cell Movement Cell Proliferation Cysteine-Rich Protein 61 / genetics* Cysteine-Rich Protein 61 / metabolism Disease Progression Female Gene Expression Regulation, Neoplastic Humans Liver Neoplasms / genetics Liver Neoplasms / metabolism Liver Neoplasms / pathology* Male Mice Neoplasm Transplantation Sequence Analysis, RNA Tissue Array Analysis Transcription Initiation Site Transfection Up-Regulation*|
|Human and Animal Cells||HuH-7|