SYT7 accelerates nasopharyngeal carcinoma progression via ALDH1A3-mediated STAT3 signaling activation.

Abstract

Nasopharyngeal carcinoma (NPC) is a special histological and ethical type of head and neck cancer with unsatisfactory clinical outcome. Thus, exploring effective molecular targets is critical for NPC treatment. We observed increased expression levels of synaptotagmin-7 (SYT7) in NPC tissues, which correlated with unfavorable prognoses. Furthermore, knockdown of SYT7 in NPC cells suppressed proliferation and migration rates, and enhanced apoptosis. In contrast, overexpression of SYT7 accelerated NPC tumor growth. Using whole-genome gene arrays and immunoprecipitation-mass spectrometry assays, aldehyde dehydrogenase 1 family member A3 (ALDH1A3), a regulator of glycolytic metabolism, was identified as a critical downstream target of SYT7. Mechanistically, SYT7 binds and promotes ALDH1A3 deubiquitination, resulting in decreased ALDH1A3 degradation. Notably, we also observed an increased expression of ALDH1A3 in NPC. More importantly, the knockdown of ALDH1A3 resulted in suppressed proliferation, migration, glycolysis, and promoted apoptosis, all of which could be restored by the overexpression of SYT7 in NPC cells. Taken together, we found that SYT7 increases ALDH1A3-mediated STAT3 activation and glycolysis, contributing to NPC progression, which provides a possible molecular mechanism for the development of targeted therapeutics interventions.