ZNF507 affects TGF-β signaling via TGFBR1 and MAP3K8 activation in the progression of prostate cancer to an aggressive state

Abstract

Background The progression of prostate cancer (PC) to the highly aggressive metastatic castration-resistant prostate cancer (mCRPC) or neuroendocrine prostate cancer (NEPC) is a fatal condition and the underlying molecular mechanisms are poorly understood. Here, we identified the novel transcriptional factor ZNF507 as a key mediator in the progression of PC to an aggressive state. Methods We analyzed ZNF507 expression in the data from various human PC database and high-grade PC patient samples. By establishment of ZNF507 knockdown and overexpression human PC cell lines, we assessed in vitro PC phenotype changes including cell proliferation, survival, migration and invasion. By performing microarray with ZNF507 knockdown PC cells, we profiled the gene clusters affected by ZNF507 knockdown. Moreover, ZNF507 regulated key signal was evaluated by dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. Finally, we performed xenograft and in vivo metastasis assay to confirm the effect of ZNF507 knockdown in PC cells. Results We found that ZNF507 expression was increased, particularly in the highly graded PC. ZNF507 was also found to be associated with metastatic PC of a high grade. Loss- or gain-of-function–based analysis revealed that ZNF507 promotes the growth, survival, proliferation, and metastatic properties of PC (e.g., epithelial-mesenchymal transition) by upregulating TGF-β signaling. Profiling of gene clusters affected by ZNF507 knockdown revealed that ZNF507 positively regulated the transcription of TGFBR1, MAP3K8, and FURIN, which in turn promoted the progression of PC to highly metastatic and aggressive state. Conclusions Our findings suggest that ZNF507 is a novel key regulator of TGF-β signaling in the progression of malignant PC and could be a promising target for studying the development of advanced metastatic PCs.

Genomic Regions and Candidate Genes Affecting Response to Heat Stress with Newcastle Virus Infection in Commercial Layer Chicks Using Chicken 600K Single Nucleotide Polymorphism Array

“…Within these candidate genes, zinc finger protein 507 (ZNF507) was significantly upregulated in Fayoumi livers with chronic heat stress combined with NDV infection. ZNF507 is predicted to facilitate DNA binding and metal ion binding activities, and can regulate transcription in mammals [ 63 ]. Whether higher expression levels of ZNF507 correlated with lower BE levels indicate heat resilience should be further investigated.…”

Epigenetic Regulation of MAP3K8 in EBV-Associated Gastric Carcinoma

“…MAP3K8 could promote myeloma progression by TNFα-mediated ERK activation [31]. ZNF507 mediated transcriptional regulation of MAP3K8 accelerated the progression of prostate cancer to a highly metastatic and aggressive state [32]. MAP3K8 also acts as a prognostic biomarker for various cancers including, renal clear cell carcinoma, glioma, and high-grade serous ovarian carcinomas [33][34][35].…”