Roles of the HOXA10 gene during castrate-resistant prostate cancer progression

Zhi Long, Yinan Li, Yu Gan, Dongyu Zhao, Guangyu Wang, Ning Xie, Jessica M. Lovnicki, Ladan Fazli, Qi Cao, Kaifu Chen, Xuesen Dong

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Homeobox A10 (HOXA10) is an important transcription factor that regulates the development of the prostate gland. However, it remains unknown whether it modulates prostate cancer (PCa) progression into castrate-resistant stages. In this study, we have applied RNA in situ hybridization assays to demonstrate that downregulation of HOXA10 expression is associated with castrate-resistant PCa. These findings are supported by public RNA-seq data showing that reduced HOXA10 expression is correlated with poor patient survival. We show that HOXA10 suppresses PCa cell proliferation, anchorage colony formation and xenograft growth independent to androgens. Using AmpliSeq transcriptome sequencing, we have found that gene groups associated with lipid metabolism and androgen receptor (AR) signaling are enriched in the HOXA10 transcriptome. Furthermore, we demonstrate that HOXA10 suppresses the transcription of the fatty acid synthase (FASN) gene by forming a protein complex with AR and prevents AR recruitment to the FASN gene promoter. These results lead us to conclude that downregulation of HOXA10 gene expression may enhance lipogenesis to promote PCa cell growth and tumor progression to castrate-resistant stage.

Original languageEnglish (US)
Pages (from-to)279-292
Number of pages14
JournalEndocrine-Related Cancer
Volume26
Issue number3
DOIs
StatePublished - Mar 2019

Keywords

  • Castrate-resistant prostate cancer
  • FASN
  • HOXA10
  • Lipid synthesis and androgen receptor

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

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