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.

中文翻译：

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DJ-1通过抑制JNK–Bcl2–Beclin1信号传导抑制前列腺癌细胞的自噬活性

DJ-1对AR信号的调控在前列腺癌（PCa）的发病机理中起着重要作用。DJ-1可能通过依赖JNK的途径改变自噬并调节Beclin1参与的自噬反应。已知JNK通过Bcl2-Beclin1复合体介导自噬。因此，本研究旨在研究自噬在DJ-1调节的PCa细胞中的重要性。目前的研究表明，LNCaP中DJ-1的过表达降低了LC3的转化和自噬体的形成。但是，DJ-1组合发挥了相反的作用。此外，DJ-1沉默可抑制LNCaP的存活并促进其死亡，可通过3-MA的自噬抑制来恢复。此外，DJ-1过表达抑制JNK和Bcl2的磷酸化以及Beclin1和Bcl2的解离。使DJ-1静音的效果完全相反。更重要的是，被茴香霉素激活的JNK抑制了DJ-1过表达的LNCaP的增殖并促进了其死亡，同时增加了LC3转化和LC3点形成，但这些结果被Beclin1的减少（由spautin-1）所逆转。相反，当DJ-1沉默时，JNK抑制剂SP600125抑制LNCaP的死亡，LC3转化和LC3点形成，从而促进细胞增殖。但是，Bcl2抑制（通过ABT737）可以逆转SP600125的所有作用。我们的结果表明，PCa细胞中的DJ-1可以通过自噬抑制促进PCa的生长，而JNK–Bcl2–Beclin1信号在其中起着重要作用。该研究为DJ-1在PCa开发中的作用提供了新见解。被茴香醚激活的JNK抑制了DJ-1过表达的LNCaP的增殖并促进了其死亡，同时增加了LC3转化和LC3点形成，但Beclin1的减少（由spautin-1）逆转了这些结果。相反，当DJ-1沉默时，JNK抑制剂SP600125抑制LNCaP的死亡，LC3转化和LC3点形成，从而促进细胞增殖。但是，Bcl2抑制（通过ABT737）可以逆转SP600125的所有作用。我们的结果表明，PCa细胞中的DJ-1可以通过自噬抑制促进PCa的生长，而JNK–Bcl2–Beclin1信号在其中起着重要作用。该研究为DJ-1在PCa开发中的作用提供了新见解。被茴香醚激活的JNK抑制了DJ-1过表达的LNCaP的增殖并促进了其死亡，同时增加了LC3转化和LC3点形成，但Beclin1的减少（由spautin-1）逆转了这些结果。相反，当DJ-1沉默时，JNK抑制剂SP600125抑制LNCaP的死亡，LC3转化和LC3点形成，从而促进细胞增殖。但是，Bcl2抑制（通过ABT737）可以逆转SP600125的所有作用。我们的结果表明，PCa细胞中的DJ-1可以通过自噬抑制促进PCa的生长，而JNK–Bcl2–Beclin1信号在其中起着重要作用。该研究为DJ-1在PCa开发中的作用提供了新见解。