Abstract
BackgroundAutophagy 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. Here, we investigated the function of YY1 in pancreatic cancer cells autophagy and its mechanisms of action.MethodsThe activity of cells undergoing autophagy was assessed using transmission electron microscopy, immunofluorescence, 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.ResultsYY1 was confirmed to regulate autophagy in pancreatic cancer cells. It was found to directly regulate the expression of miR-30a, a known modulator of autophagy-associated genes. Furthermore, overexpression of miR-30a attenuated the pro-autophagic effects of YY1.ConclusionsCumulatively, 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 findings provide a potential druggable target for the development of treatments for pancreatic cancer.
Highlights
Autophagy is a highly regulated biological process that mediates the degradation of intracellular com‐ ponents
We clearly demonstrate that Yin-Yang 1 (YY1) modulates autophagy in pancreatic cancer cells by directly targeting miR-30a, an established regulator of the autophagy-associated genes, ATG5 and Beclin 1 [18, 19]
YY1 is implicated in autophagy in pancreatic cancer cells During autophagosome formation, the cytosolic microtubule-associated protein 1 light chain 3 (LC3)I is converted into LC3-II, it is phosphatidylethanolamine- conjugated form
Summary
Autophagy is a highly regulated biological process that mediates the degradation of intracellular com‐ ponents It is required for tumor cell metabolism and homeostasis. The term “Yin-Yang” refers to its two opposing functions as either a transcriptional repressor or transcriptional activator during tumorigenesis It has fundamental roles in embryogenesis, cell proliferation, and differentiation, which strongly suggests a potentially important function for YY1 during cancer development and progression [2]. Autophagy has recently gained considerable attention by researchers It is a highly regulated biological mechanism that facilitates the degradation of intracellular materials within autophagosomes by delivering them to lysosomes for bulk degradation. Several studies have reported that autophagy protects pancreatic cancer cells from drugs and environmental stress [14, 15]. The relationship between YY1 and autophagy in pancreatic cancer cells has not been reported
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