Frontiers in Oncology (Jul 2020)
RBFOX3 Promotes Gastric Cancer Growth and Progression by Activating HTERT Signaling
- Chen Luo,
- Chen Luo,
- Chen Luo,
- Xiaojian Zhu,
- Xiaojian Zhu,
- Xiaojian Zhu,
- Qilin Luo,
- Fanqin Bu,
- Fanqin Bu,
- Fanqin Bu,
- Chao Huang,
- Chao Huang,
- Chao Huang,
- Jingfeng Zhu,
- Jingfeng Zhu,
- Jingfeng Zhu,
- Jiefeng Zhao,
- Jiefeng Zhao,
- Jiefeng Zhao,
- Wenjun Zhang,
- Wenjun Zhang,
- Wenjun Zhang,
- Kang Lin,
- Kang Lin,
- Kang Lin,
- Cegui Hu,
- Cegui Hu,
- Zeng Zong,
- Zeng Zong,
- Hongliang Luo,
- Hongliang Luo,
- Jun Huang,
- Zhengming Zhu
Affiliations
- Chen Luo
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Chen Luo
- Department of Clinical Medical, Jiangxi Medical College of Nanchang University, Nanchang, China
- Chen Luo
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China
- Xiaojian Zhu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Xiaojian Zhu
- Department of Clinical Medical, Jiangxi Medical College of Nanchang University, Nanchang, China
- Xiaojian Zhu
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China
- Qilin Luo
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Fanqin Bu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Fanqin Bu
- Department of Clinical Medical, Jiangxi Medical College of Nanchang University, Nanchang, China
- Fanqin Bu
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China
- Chao Huang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Chao Huang
- Department of Clinical Medical, Jiangxi Medical College of Nanchang University, Nanchang, China
- Chao Huang
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China
- Jingfeng Zhu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Jingfeng Zhu
- Department of Clinical Medical, Jiangxi Medical College of Nanchang University, Nanchang, China
- Jingfeng Zhu
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China
- Jiefeng Zhao
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Jiefeng Zhao
- Department of Clinical Medical, Jiangxi Medical College of Nanchang University, Nanchang, China
- Jiefeng Zhao
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China
- Wenjun Zhang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Wenjun Zhang
- Department of Clinical Medical, Jiangxi Medical College of Nanchang University, Nanchang, China
- Wenjun Zhang
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China
- Kang Lin
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Kang Lin
- Department of Clinical Medical, Jiangxi Medical College of Nanchang University, Nanchang, China
- Kang Lin
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China
- Cegui Hu
- Department of Clinical Medical, Jiangxi Medical College of Nanchang University, Nanchang, China
- Cegui Hu
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China
- Zeng Zong
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Zeng Zong
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China
- Hongliang Luo
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Hongliang Luo
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China
- Jun Huang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Zhengming Zhu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- DOI
- https://doi.org/10.3389/fonc.2020.01044
- Journal volume & issue
-
Vol. 10
Abstract
Tumor invasion, metastasis, and recrudescence remain a considerable challenge in the treatment of gastric cancer (GC). Herein we first identified that RNA binding protein fox-1 homolog 3 (RBFOX3) was markedly overexpressed in GC tissues and negatively linked to the survival rate of GC patients. RBFOX3 promoted cell division and cell cycle progression in vitro and in vivo. Furthermore, RBFOX3 increased the cell invasion and migration ability. The suppression of GC cell multiplication and invasion, caused by silencing of RBFOX3, was rescued by HTERT overexpression. Additionally, RBFOX3 augmented the resistance of GC cells to 5-fluorouracil by repressing RBFOX3. Mechanistically, the exogenous up-regulation of RBFOX3 triggered promoter activity and HTERT expression, thereby enhancing the division and the development of GC cells. Further co-immunoprecipitation tests revealed that RBFOX3 bound to AP-2β to modulate HTERT expression. In conclusion, our study indicates that a high expression of RBFOX3 promotes GC progression and development and predicts worse prognosis. Collectively, these results indicate that the RBFOX3/AP-2β/HTERT signaling pathway can be therapeutically targeted to prevent and treat GC recurrence and metastasis.
Keywords