RBFOX3 Promotes Gastric Cancer Growth and Progression by Activating HTERT Signaling (Retracted Article)
RBFOX3 Promotes Gastric Cancer Growth and Progression by Activating HTERT Signaling (Retracted Article)
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DOI：
10.3389/fonc.2020.01044
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发表时间：
2020-07-20
影响因子：
4.7
通讯作者：
Zhu, Zhengming
中科院分区：
文献类型：
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作者：
Luo, Chen;Zhu, Xiaojian;Zhu, Zhengming
胃癌的侵袭、转移和复发仍然是胃癌治疗的一大挑战。在此，我们首次发现RNA结合蛋白fox-1同源物3（RBFOX 3）在GC组织中显著过表达，并与GC患者的生存率呈负相关。RBFOX 3在体外和体内均能促进细胞分裂和细胞周期进程。此外，RBFOX 3增强了细胞的侵袭和迁移能力。由RBFOX 3沉默引起的GC细胞增殖和侵袭的抑制被HTERT过表达拯救。此外，RBFOX 3通过抑制RBFOX 3增强GC细胞对5-氟尿嘧啶的抗性。机制上，外源性上调RBFOX 3触发启动子活性和HTERT表达，从而增强GC细胞的分裂和发育。进一步的免疫共沉淀试验显示，RBFOX 3与AP-2 β结合以调节HTERT表达。总之，我们的研究表明RBFOX 3的高表达促进GC的进展和发展，并预测预后不良。总的来说，这些结果表明RBFOX 3/AP-2 β/HTERT信号通路可以在治疗上靶向预防和治疗GC复发和转移。
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 progressionin vitroandin 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-2 beta 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-2 beta/HTERT signaling pathway can be therapeutically targeted to prevent and treat GC recurrence and metastasis.