Abstract
The regulation of DJ-1 on AR signaling plays an important role in the pathogenesis of prostate cancer (PCa). DJ-1 could alter autophagy and regulate Beclin1-involved autophagy response through JNK-dependent pathway. JNK is known to mediate autophagy through Bcl2-Beclin1 complex. Therefore, this study aimed to investigate the significance of autophagy in DJ-1-modulated PCa cells. The current studies showed that DJ-1 overexpression in LNCaP decreased LC3 transformation and autophagosome formation. However, DJ-1 knockdown exerted the opposite effect. Moreover, DJ-1 silencing inhibited survival and promoted death in LNCaP, which was recovered by autophagy inhibition with 3-MA. In addition, DJ-1 overexpression inhibited the phosphorylation of JNK and Bcl2, and the dissociation of Beclin1 and Bcl2; while the effect of silencing DJ-1 was completely opposite. More important, JNK activated by anisimycin inhibited the proliferation and promoted death of DJ-1-overexpressed LNCaP while increasing LC3 transformation and LC3-puncta formation, but these results were reversed by the decrease of Beclin1 (by spautin-1). In contrast, when DJ-1 was silenced, the death of LNCaP, LC3 transformation, and LC3-puncta formation were inhibited by JNK inhibitor SP600125, which promoted cell proliferation. However, Bcl2 inhibition (by ABT737) reversed all the effects of SP600125. Our results suggested that DJ-1 in PCa cells could promote the growth of PCa through autophagy inhibition, and JNK-Bcl2-Beclin1 signaling played an important role in it. The study provided new insights into the role of DJ-1 in the development of PCa.