Hormone therapy drugs, such as bicalutamide and enzalutamide, directed against prostate cancer focus on androgen receptor (AR) signaling and are initially effective, but the disease progresses to lethality as resistance to these drugs develops. A method to prolong the drug response time and improve the drug efficacy is still unavailable. TRIM36 was reported as a novel androgen signaling target gene and is upregulated in prostate cancer. In this study, we found that 63.4% (64/95) of PCa in TMA expressed the TRIM36 protein. Interestingly, patients with negative TRIM36 expression had a shorter biochemical recurrence-free survival. TRIM36 expression was significantly associated with the Gleason score (P = 0.005), delayed prostate cancer cell cycle progression and inhibited cell proliferation in vitro and in vivo, and these effects were mediated via inhibition of the MAPK/ERK phosphorylation pathway. Remarkably, we found that rescuing the expression of TRIM36 during anti-androgen therapy could improve the drug efficacy. Collectively, TRIM36 is a novel androgen-responsive gene, and it dramatically enhanced the efficacy of anti-androgen drugs against prostate cancer.

Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.

Background: Ubiquitylation modification is one of the multiple post-transcriptional process to regulate cellular physiology, including cell signaling, cycle regulation, DNA repair and transcriptional regulation. Members of TRIM family proteins could be defined as E3 ubiquitin ligases as they contain a RING-finger domain, and alterations of TRIM proteins are involved into a broad range of diverse disorders including cancer. TRIM37 is a novel discovered E3 ubiquitin ligase and acts as a oncoprotein in multiple human neoplasms, however its biological role in RCC still remains elusive.Methods: RCC microarray chips and public datasets were screened to identify novel TRIMs member as TRIM37, which was dysregulated in RCC. Gain or loss of functional cancer cell models were constructed, and in vitro and in vivo assays were performed to elucidate its tumorigenic phenotypes. Interactive network analyses were utilized to define intrinsic mechanism.Results: We identified TRIM37 was upregulated in RCC tumors, and its aberrant function predicted aggressive neoplastic phenotypes, poorer survival endings. TRIM37 promoted RCC cells EMT and malignant progression via TGF-β1 signaling activation, as a consequence of directly mediated by ubiquitinating-H2A modifications.Conclusions: Our findings identified a previously unappreciated role of TRIM37 in RCC progression and prognostic prediction. Importantly, we declared a novel ubiquitination-dependent link between TRIM ubiquitin ligases and TGF-β1 signaling in regulating cancerous malignancies.

The mRNA expression of CAPN2 was upregulated in CRPC cells (DU145 and PC3) than that in non-CRPC cells. Silencing CAPN2 expression could inhibit DU145 and PC3 cells proliferation by cell cycle arrest at G1 phase. Knockdown of CPAN2 level suppressed the migration and invasion capacity of CRPC cells by reducing matrix metalloproteinase-2 (MMP-2) and MMP-9 activation, as well as repressing the phosphorylation protein expression of AKT and mTOR. In addition, we found that the expression of CAPN2 was elevated in Pca tissues than that in normal control tissues. Therefore, we showed the important roles of CAPN2 in the development and progression in CRPC cells, suggesting a new therapeutic intervention for treating castration-resistant prostate cancer patients.