The PTB-Associated Splicing Factor/Peroxisome Proliferator-Activated Receptor Gamma Axis Regulates Autophagosome Formation in Human Pancreatic Cancer Cells

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor that plays a major regulatory role in metabolic function. It is overexpressed in many types of cancer cells, suggesting that regulation of PPARγ may also affect carcinogenesis. Our previous study suggested that PTB-associated splicing factor (PSF) is a PPARγ-interacting protein and growth regulator of colon cancer cells. In addition, PSF has been shown to be involved in several important regulatory steps of cancer cell proliferation. In this study, we aimed to investigate the relationships between PSF and PPARγ in pancreatic cancer by evaluating the effects of PSF expression in pancreatic cancer cell lines. PSF expression affected the expression of PPARγ, and knockdown of PSF using specific small-interfering RNA (siRNA) significantly suppressed the proliferation of pancreatic cancer cells. Furthermore, PSF knockdown induced cell growth inhibition and autophagosome formation through inhibition of PPARγ. Interestingly, Panc-1 cells were more susceptible to PSF knockdown-induced autophagy than MIA-PaCa-2 cells. Thus, our data indicated that PSF was an important regulator of autophagy and played critical roles in the survival and growth of pancreatic cancer cells. The PSF-PPARγ axis may play a role in the control of pancreatic cancer pathogenesis. This study is the first to describe the effects of PSF on pancreatic cancer cell growth and autophagy associated with PPARγ.