A Yin-Yang 1/miR-30a Regulatory Circuit Modulates Autophagy In Pancreatic Cancer Cells

Background:Autophagy is a highly regulated biological process that mediates the degradation of intracellular components.It is required for tumor cell metabolism and homeostasis.Yin?Yang 1(YY1)has been reported to be involved in autophagy in several carcinomas.However,its role in autophagy in pancreatic cancer,one of the deadliest human malignancies,is unknown.Objective:To investigated the function of YY1 in pancreatic cancer cells autophagy and its mechanisms of action.Methods:The activity of cells undergoing autophagy was assessed using transmission electron microscopy,immunofuorescence,and Western blotting.A luciferase activity assay,real?time quantitative polymerase chain reaction(RT?qPCR),and chromatin immunoprecipitation(ChIP)were also used to identify putative downstream targets of YY1.Results:YY1 was confrmed to regulate autophagy in pancreatic cancer cells.It was found to directly regulate the expression of miR30 a,a known modulator of autophagy?associated genes.Furthermore,overexpression of mi R30 a attenuated the pro?autophagic efects of YY1.Conclusion:Cumulatively,our data suggest that miR?30a acts in a feedback loop to modulate the pro?autophagic activities of YY1.Thus,autophagy in pancreatic cancer cells may be regulated,in part,by a tightly coordinated YY1/miR?30a regulatory circuit.These fndings provide a potential druggable target for the development of treatments for pancreatic cancer.