Preprint Article Version 1 This version is not peer-reviewed

RBFOX3 Promotes Gastric Cancer Growth and Progression through Activating HTERT Signaling

Version 1 : Received: 12 April 2020 / Approved: 16 April 2020 / Online: 16 April 2020 (08:17:44 CEST)

How to cite: Luo, C.; zhu, X.; Luo, Q.; Bu, F.; Huang, C.; zhu, J.; zhao, J.; zhao, W.; Lin, K.; Hu, C.; Zong, Z.; Luo, H.; Huang, J.; Zhu, Z. RBFOX3 Promotes Gastric Cancer Growth and Progression through Activating HTERT Signaling. Preprints 2020, 2020040264 (doi: 10.20944/preprints202004.0264.v1). Luo, C.; zhu, X.; Luo, Q.; Bu, F.; Huang, C.; zhu, J.; zhao, J.; zhao, W.; Lin, K.; Hu, C.; Zong, Z.; Luo, H.; Huang, J.; Zhu, Z. RBFOX3 Promotes Gastric Cancer Growth and Progression through Activating HTERT Signaling. Preprints 2020, 2020040264 (doi: 10.20944/preprints202004.0264.v1).

Abstract

Tumor invasion, metastasis, and recrudesce remain a considerable challenge in the treatment of gastric cancer (GC). Herein, we first identified that RBFOX3 (RNA binding protein fox-1 homolog 3) was significantly up-regulated in GC tissues and negatively linked to the survival rate of GC patients. RBFOX3 promoted cell division and cell cycle progression in vitro as well as in vivo. Furthermore, RBFOX3 increased cell invasion and migration ability. Interestingly, both the suppression of GC cell multiplication and invasion moderated by the silencing of RBFOX3 was rescued by HTERT up-regulation. Additionally, RBFOX3 augmented the resistance of GC cells to 5-fluorouracil (5-Fu) by repressing RBFOX3. Mechanistically, exogenous up-regulation of RBFOX3 triggered promoter activity and HTERT expression thereby enhancing the division and development of GC cells. Importantly, our findings revealed that RBFOX3 interacted with AP-2β to modulate the HTERT expression as demonstrated by co-immunoprecipitation analysis. In conclusion, our study indicates that high expression of RBFOX3 promotes GC progression and development but predicts worse prognosis by stimulating HTERT signaling. Moreover, the results suggest that the RBFOX3/AP-2β/HTERT pathway is a novel target for the development of therapeutic agents for the prevention and treatment of GC reappearance and metastasis.

Subject Areas

RBFOX3; HTERT; gastric cancer; promoter-binding protein; cancer biomarker

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