Gong Zhongqin, Jia Hao, Yu Jianqing, Liu Yi, Ren Jianwei, Yang Shengli, Hu Baoguang, Liu Liping, Lai Paul B S, Chen George Gong
Department of Surgery, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
Department of Thyroid and Breast Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, Guangdong, China.
Oncogenesis. 2020 Oct 28;9(10):97. doi: 10.1038/s41389-020-00283-x.
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.
叉头框蛋白P3（FOXP3）及其异构体在肝细胞癌（HCC）中的状态尚不清楚。我们旨在研究FOXP3及其异构体在HCC中的表达和功能。该研究对84例HCC患者、HCC细胞系和小鼠肿瘤模型进行。通过巢式PCR、定量实时PCR和免疫组织化学（IHC）染色来测定FOXP3及其异构体的水平。分析了它们的水平与临床病理特征之间的相关性。发现全长FOXP3（FOXP3）和第3外显子缺失的FOXP3（FOXP3Δ3）是HCC中的主要异构体。HCC肿瘤样本中FOXP3Δ3 mRNA和蛋白的水平与其相邻正常组织相比无显著差异。HCC患者中FOXP3蛋白的高表达显示出良好的总生存期。FOXP3的过表达显著降低肿瘤细胞的增殖、迁移和侵袭。免疫荧光结果表明，FOXP3需要转位到细胞核中才能发挥其抑制功能。荧光素酶测定表明，FOXP3可与Smad2/3/4协同抑制癌基因c-Myc。免疫共沉淀结果进一步显示，FOXP3可与Smad2/3/4相互作用。染色质免疫沉淀（ChIP）测定表明，FOXP3和Smad2/3/4均与c-Myc的启动子结合以抑制它。体内小鼠肿瘤模型研究证实了FOXP3的抑制作用。总的来说，肿瘤FOXP3的表达可通过直接抑制c-Myc或通过与Smad2/3/4相互作用间接抑制c-Myc来抑制HCC的生长。因此，FOXP3是HCC中的一种肿瘤抑制因子。
Zotero 插件
