Targeting GABARAPL1/HIF-2a in nasopharyngeal carcinoma

Abstract

Abstract The primary gene mutations associated with nasopharyngeal carcinoma (NPC) are located within phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling pathways. These pathways have inhibitory effects on autophagy, and autophagy has become an important area of NPC research. However, the potential molecular targets related to autophagy in NPC remain to be elucidated. The current study examined levels of autophagy-related genes, including autophagy related 4B cysteine peptidase (ATG4B) and gamma aminobutyric acid (GABA) type A receptor associated protein like 1 (GABARAPL1), in nasopharyngeal carcinoma tissues and explored their potential role as novel targets for the treatment of NPC. Overexpression of GABARAPL1 was shown to decrease the level of hypoxia-inducible factor (HIF)-2α and induce apoptosis in NPC cells. Importantly, when nude mice were subcutaneously inoculated with NPC cells, overexpression of GABARAPL1 slowed tumor growth. Furthermore, the underlying mechanism by which GABARAPL1 regulated nasopharyngeal tumor growth was investigated. HIF-2α, as a substrate for autophagic degradation, may play an interesting role during NPC progression. This study highlighted novel targets that may be used to treat NPC patients in the future.