Nuclear FOXP3 inhibits tumor growth and induced apoptosis in hepatocellular carcinoma by targeting c-Myc
| Autor: | Shengli Yang, Jianqing Yu, Hao Jia, Jianwei Ren, Paul B.S. Lai, Liping Liu, Bao-guang Hu, George G. Chen, Yi Liu, Zhongqin Gong |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Gene isoform Cancer Research chemical and pharmacologic phenomena Immunofluorescence lcsh:RC254-282 Article 03 medical and health sciences 0302 clinical medicine medicine Molecular Biology medicine.diagnostic_test Oncogene Chemistry hemic and immune systems lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease digestive system diseases 030104 developmental biology Cell culture Apoptosis 030220 oncology & carcinogenesis Hepatocellular carcinoma Cancer research Immunohistochemistry Liver cancer Chromatin immunoprecipitation Cell signalling |
| Zdroj: | Oncogenesis Oncogenesis, Vol 9, Iss 10, Pp 1-11 (2020) |
| ISSN: | 2157-9024 |
| DOI: | 10.1038/s41389-020-00283-x |
| Popis: | The status of FOXP3 and its isoforms in hepatocellular carcinoma (HCC) is unclear. We aimed to investigate the expression and function of FOXP3 and its isoforms in HCC. The study was performed on 84 HCC patients, HCC cell lines and a mouse tumor model. The levels of FOXP3 and its isoforms were determined by nested PCR, quantitative real-time PCR and immunohistochemistry (IHC) staining. The correlation between their levels and clinicopathologic characteristics was analyzed. The full length of FOXP3 (FOXP3) and exon 3-deleted FOXP3 (FOXP3Δ3) were found to be the major isoforms in HCC. The levels of FOXP3Δ3 mRNA and protein in HCC tumor samples were not significantly different from their adjacent normal tissues. The high expression of FOXP3 protein in HCC patients showed a good overall survival. The overexpression of FOXP3 significantly reduced tumor cell proliferation, migration and invasion. The immunofluorescence result indicated that FOXP3 needed to be translocated into the nucleus to exert its inhibitory function. The luciferase assay demonstrated that FOXP3 could be synergistic with Smad2/3/4 to inhibit the oncogene c-Myc. The co-immunoprecipitation results further revealed that FOXP3 could interact with Smad2/3/4. The chromatin immunoprecipitation (ChIP) assay showed that both FOXP3 and Smad2/3/4 bound the promoter of the c-Myc to inhibit it. The in vivo mouse tumor model study confirmed the inhibitory effect of FOXP3. Collectively, the expression of tumor FOXP3 can inhibit the growth of HCC via suppressing c-Myc directly or indirectly via interacting with Smad2/3/4. Therefore, FOXP3 is a tumor suppressor in HCC. |
| Databáze: | OpenAIRE |
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