Jiwei Wang1, Song Li2, Honglang Li3, Xiaoshuang Zhou3, Huabin Wen3, Bin Lai4. 1. Department of Ultrasound, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China. 2. Mudanjiang Medical College, Mudanjiang, Heilongjiang, China. 3. Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, No 1. Minde Road, Nanchang, Jiangxi, 330006, China. 4. Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, No 1. Minde Road, Nanchang, Jiangxi, 330006, China. Vincent83126@163.com.
Abstract
BACKGROUND: Interferon regulatory factor 4 (IRF4) is a transcription factor from the IRF factor family that exerts regulatory functions in the immune system and oncogenesis. However, the biological role of IRF4 in colon cancer is still unclear. The aim of this study is to investigate whether IRF4 participates in the immune response in colon cancer. METHODS: We compared the expression of IRF4, the number of regulatory T cells (Tregs) and macrophages in the colon cancer tissues and paracancerous colon tissues from colon cancer patients. Colon cancer mouse model was established by inoculation with colon cancer cells (SW480) as a xenograft tumor, and we observed tumor growth of colon cancer. Furthermore, the mechanism of action of IRF4 in transdifferentiation of Tregs into macrophage-like cells and the effect of IRF4 on colon cancer cells were investigated in vitro. RESULTS: IRF4 was severely down-regulated in the colon cancer tissues. Colon cancer tissues exhibited an increase in the number of regulatory T cells (Tregs) and macrophages. Furthermore, IRF4 overexpression repressed proliferation, migration and invasion of colon cancer cells (SW480 and HT116 cells). Moreover, IRF4 up-regulation ameliorated tumor growth of colon cancer by promoting the transdifferentiation of Tregs into macrophage-like cells through inhibition of BCL6 expression. Exosomes derived from colon cancer cells repressed IRF4 expression in Tregs by transmitting miR-27a-3p, miR-30a-5p and miR-320c. CONCLUSIONS: IRF4 overexpression promoted the transdifferentiation of Tregs into macrophage-like cells to inhibit the occurrence and development of colon cancer. Thus, IRF4 may be a potential target for colon cancer treatment.
BACKGROUND:Interferon regulatory factor 4 (IRF4) is a transcription factor from the IRF factor family that exerts regulatory functions in the immune system and oncogenesis. However, the biological role of IRF4 in colon cancer is still unclear. The aim of this study is to investigate whether IRF4 participates in the immune response in colon cancer. METHODS: We compared the expression of IRF4, the number of regulatory T cells (Tregs) and macrophages in the colon cancer tissues and paracancerous colon tissues from colon cancerpatients. Colon cancermouse model was established by inoculation with colon cancer cells (SW480) as a xenograft tumor, and we observed tumor growth of colon cancer. Furthermore, the mechanism of action of IRF4 in transdifferentiation of Tregs into macrophage-like cells and the effect of IRF4 on colon cancer cells were investigated in vitro. RESULTS:IRF4 was severely down-regulated in the colon cancer tissues. Colon cancer tissues exhibited an increase in the number of regulatory T cells (Tregs) and macrophages. Furthermore, IRF4 overexpression repressed proliferation, migration and invasion of colon cancer cells (SW480 and HT116 cells). Moreover, IRF4 up-regulation ameliorated tumor growth of colon cancer by promoting the transdifferentiation of Tregs into macrophage-like cells through inhibition of BCL6 expression. Exosomes derived from colon cancer cells repressed IRF4 expression in Tregs by transmitting miR-27a-3p, miR-30a-5p and miR-320c. CONCLUSIONS:IRF4 overexpression promoted the transdifferentiation of Tregs into macrophage-like cells to inhibit the occurrence and development of colon cancer. Thus, IRF4 may be a potential target for colon cancer treatment.
Authors: Arthur L Shaffer; N C Tolga Emre; Laurence Lamy; Vu N Ngo; George Wright; Wenming Xiao; John Powell; Sandeep Dave; Xin Yu; Hong Zhao; Yuxin Zeng; Bangzheng Chen; Joshua Epstein; Louis M Staudt Journal: Nature Date: 2008-06-22 Impact factor: 49.962
Authors: Ashutosh Chaudhry; Dipayan Rudra; Piper Treuting; Robert M Samstein; Yuqiong Liang; Arnold Kas; Alexander Y Rudensky Journal: Science Date: 2009-10-01 Impact factor: 47.728