No abstract

Background: The androgen receptor (AR) signaling pathway has been well demonstrated to play a crucial role in the development, progression, and drug resistance of prostate cancer. Although the current anti-androgen therapy could significantly benefit prostate cancer patients initially, the efficacy of the single drug usually lasts for a relatively short period, as drug resistance quickly emerges. Methods:We have performed an unbiased bioinformatics analysis using the RNAseq results in 22Rv1 cells to identify the cell response toward Dip G treatment. The RNA-seq results were validated by qRT-PCR. Protein levels were detected by western blot or staining. Cell viability was measured by Aquabluer and colony formation assay. Results: Here, we identified that Diptoindonesin G (Dip G), a natural extracted compound, could promote the proteasome degradation of AR and polo-like kinase 1 (PLK1) through modulating the activation of CHIP E3 ligase. Administration of Dip G has shown a profound efficiency in the suppression of AR and PLK1, not only in androgen-dependent LNCaP cells but also in castration-resistant and enzalutamideresistant cells in a CHIP-dependent manner. Through co-targeting the AR signaling, Dip G robustly improved the efficacy of HSP90 inhibitors and enzalutamide in both human prostate cancer cells and in vivo xenograft mouse model. Conclusions: Our results revealed that Dip G-mediated AR degradation would be a promising and valuable therapeutic strategy in the clinic.

Cover Caption: The cover image is based on the Original Article Diptoindonesin G antagonizes AR signaling and enhances the efficacy of antiandrogen therapy in prostate cancer by Fengyi Mao et al., https://doi.org/10.1002/pros.24336

BnSIP1-1 is the first identified SIP1 (6b Interacting Protein1) subfamily gene of the trihelix transcription factor family from Brassica napus (B. napus). We previously used a reverse genetic method to reveal its abiotic stress response function in endowing plants resistance to drought and salinity, as well as ABA (Abscisic acid). However, the molecular mechanisms of BnSIP1-1 are unclear. In this study, the global transcriptome files of BnSIP1-1-overexpressing transgenic and wildtype B. napus seedlings under ABA treatment were constructed using RNA-seq. A total of 1823 and 5512 DEGs (Differentially Expressed Genes) were identified in OE vs. WT and OE_ABA vs. WT_ABA comparison groups, which included 751 and 2567 up-regulated DEGs, and 1072 and 2945 down-regulated DEGs, separately. The impact of overexpressed BnSIP1-1 on plants was amplified by ABA, indicating BnSIP1-1 was an ABA-conditioned responsive gene. More interestingly, we found the reasons for BnSIP1-1 increasing plants’ insensitivity to ABA were not by regulating ABA synthesis and catabolism, but by manipulating ABA transportation, ABA signal perception and transduction, inositol phosphate metabolism, as well as endomembrane trafficking, indirectly suggesting this gene may play roles upstream of the core ABA response pathway. Our results provided new insights into improving the knowledge about the function of BnSIP1-1 and the ABA signaling mechanism in B. napus.