The Function And Molecular Mechanism Of GNIP1 In Regulating Autophagy In Non-small Cell Lung Cancer

Autophagy is a process that degradating the damaged or redundant proteins and organelles by lysosomes under the stimulation of nutrient deficiency and maintain the physiological balance of cells.Both Atg6(BECN1)and Atg8(LC3)are important autophagy-related proteins.BECN1 is an important component of autophagy core complex,which is crucial for autophagy activation.LC3 B is involved in the formation of preautophagosome and autophagosome membrane,and is a marker protein for autophagosome formation.GNIP1 is a member of GNIP family of glycogen interaction protein with the longest gene sequence and the largest molecular weight.At present,its research mainly focuses on glycogen self-glycosylation,E3 ubiquitin ligase activity and other aspects,little is known about its role in tumor progression and the association with autophagy is unknown.In this study,we found that the overexpression of GNIP1 could promote the proliferation and migration of non-small cell lung cancer cells through growth and scratch experiments.Through morphological observation and detection of autophagy related markers,we found that autophagy coild be induced by over-expression of GNIP1 in non-small cell lung cancer cells.We further discovered that GNIP1 was specifically bound to BECN1 and LC3 B,proving the hypothesis that GNIP1,as a scaffold protein,played an important role in the formation of autophagosomes.In addition,we clarified the specific binding sites of BECN1 and LC3 B with GNIP1 through gene cloning and immunoprecipitation experiments.In summary,these studies for the first time found a link between GNIP1 and autophagy,and elucidated the molecular mechanism of GNIP1 regulating the proliferation and migration of non-small cell lung cancer cells through autophagy,providing the theoretical foundation for targeting GNIP1 as a new therapeutic target for the development of anti-tumor drugs.