ATF3 inhibits the tumorigenesis and progression of hepatocellular carcinoma cells via upregulation of CYR61 expression
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2018-10-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
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| Online Access: | http://link.springer.com/article/10.1186/s13046-018-0919-8 |
| _version_ | 1818310589248700416 |
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| author | Cong Chen Chao Ge Zheng Liu Liangyu Li Fangyu Zhao Hua Tian Taoyang Chen Hong Li Ming Yao Jinjun Li |
| author_facet | Cong Chen Chao Ge Zheng Liu Liangyu Li Fangyu Zhao Hua Tian Taoyang Chen Hong Li Ming Yao Jinjun Li |
| author_sort | Cong Chen |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-13T07:48:28Z |
| format | Article |
| id | doaj.art-4abc019e14514b2a87ae23e68c8f0214 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-13T07:48:28Z |
| publishDate | 2018-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-4abc019e14514b2a87ae23e68c8f02142022-12-21T23:54:44ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662018-10-0137111610.1186/s13046-018-0919-8ATF3 inhibits the tumorigenesis and progression of hepatocellular carcinoma cells via upregulation of CYR61 expressionCong Chen0Chao Ge1Zheng Liu2Liangyu Li3Fangyu Zhao4Hua Tian5Taoyang Chen6Hong Li7Ming Yao8Jinjun Li9State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of MedicineState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of MedicineShanghai Medical College, Fudan UniversityShanghai Medical College, Fudan UniversityState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of MedicineState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of MedicineQidong Liver Cancer InstituteState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of MedicineState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of MedicineState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of MedicineAbstract 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.http://link.springer.com/article/10.1186/s13046-018-0919-8ATF3CYR61Hepatocellular carcinoma |
| spellingShingle | Cong Chen Chao Ge Zheng Liu Liangyu Li Fangyu Zhao Hua Tian Taoyang Chen Hong Li Ming Yao Jinjun Li ATF3 inhibits the tumorigenesis and progression of hepatocellular carcinoma cells via upregulation of CYR61 expression Journal of Experimental & Clinical Cancer Research ATF3 CYR61 Hepatocellular carcinoma |
| title | ATF3 inhibits the tumorigenesis and progression of hepatocellular carcinoma cells via upregulation of CYR61 expression |
| title_full | ATF3 inhibits the tumorigenesis and progression of hepatocellular carcinoma cells via upregulation of CYR61 expression |
| title_fullStr | ATF3 inhibits the tumorigenesis and progression of hepatocellular carcinoma cells via upregulation of CYR61 expression |
| title_full_unstemmed | ATF3 inhibits the tumorigenesis and progression of hepatocellular carcinoma cells via upregulation of CYR61 expression |
| title_short | ATF3 inhibits the tumorigenesis and progression of hepatocellular carcinoma cells via upregulation of CYR61 expression |
| title_sort | atf3 inhibits the tumorigenesis and progression of hepatocellular carcinoma cells via upregulation of cyr61 expression |
| topic | ATF3 CYR61 Hepatocellular carcinoma |
| url | http://link.springer.com/article/10.1186/s13046-018-0919-8 |
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