ABSTRACT
Macroautophagy, which will hereafter be referred to as autophagy, is an evolutionarily conserved process, during which cells recycle and remove damaged organelles and proteins in response to cellular stress. However, the mechanisms underlying the regulation of autophagy remain to be fully elucidated. The present study demonstrated that knockdown of zinc finger protein like 1 (ZFPL1) induces autophagy and increases autophagic cell death in NCIN87 and BGC823 human gastric carcinoma cell lines. To examine the role of ZFPL1 in gastric carcinoma cells, ZFPL1 expression was downregulated by lentiviral infection. Zinc finger domainFLAG was used to compete with ZFPL1 for golgin A2/GM130 binding. Autophagy was analyzed by red fluorescent proteinmicrotubuleassociated protein 1A/1Blight chain 3 (LC3) puncta, LC3I to LC3II conversion, and p62 expression. The results demonstrated that knockdown of ZFPL1 was able to significantly increase cell death rate. However, ZFPL1 knockdown exerted almost no effect on the expression of apoptosisassociated markers, including B cell lymphoma 2 (Bcl2), Bclx, Bcl2associated X protein, BH3 interacting domain death agonist, p53, and the classical caspase family members, caspase3, caspase8 and caspase9. An endogenous ZFPL1GM130 association was identified in NCIN87 cells and BGC823 cells by coimmunoprecipitation. Furthermore, cell death was restricted following treatment of ZFPL1 knockdown cells with an autophagy inhibitor. Therefore, knockdown of ZFPL1 expression may induce cell death via autophagy, rather than apoptosis. These results suggest that ZFPL1 may serve an important role in regulating autophagy in NCIN87 and BGC823 cells.