Luo Chen, Zhu Xiaojian, Luo Qilin, Bu Fanqin, Huang Chao, Zhu Jingfeng, Zhao Jiefeng, Zhang Wenjun, Lin Kang, Hu Cegui, Zong Zeng, Luo Hongliang, Huang Jun, Zhu Zhengming
Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Clinical Medical, Jiangxi Medical College of Nanchang University, Nanchang, China.
Front Oncol. 2020 Jul 20;10:1044. doi: 10.3389/fonc.2020.01044. eCollection 2020.
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 and . 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.
肿瘤侵袭、转移和复发仍然是胃癌（GC）治疗中的一个重大挑战。在此，我们首次发现RNA结合蛋白fox-1同源物3（RBFOX3）在GC组织中显著过表达，并且与GC患者的生存率呈负相关。RBFOX3促进细胞分裂和细胞周期进程。此外，RBFOX3增强了细胞侵袭和迁移能力。通过过表达HTERT挽救了因沉默RBFOX3而导致的GC细胞增殖和侵袭的抑制。此外，RBFOX3通过抑制RBFOX3增强了GC细胞对5-氟尿嘧啶的抗性。机制上，RBFOX3的外源性上调触发了启动子活性和HTERT表达，从而增强了GC细胞的分裂和发展。进一步的免疫共沉淀试验表明，RBFOX3与AP-2β结合以调节HTERT表达。总之，我们的研究表明，RBFOX3的高表达促进GC的进展和发展，并预示着更差的预后。总体而言，这些结果表明，RBFOX3/AP-2β/HTERT信号通路可作为治疗靶点，以预防和治疗GC复发和转移。
