HOTAIR is a REST-regulated lncRNA that promotes neuroendocrine differentiation in castration resistant prostate cancer

Yi-Ting Chang; Tzu-Ping Lin; Jui-Ting Tang; Mel Campbell; Yun-Li Luo; Shih-Yen Lu; Chia-Pei Yang; Ting-Yu Cheng; Ching-Hsin Chang; Tze-Tze Liu; Chi-Hung Lin; Hsing-Jein Kung; Chin-Chen Pan; Pei-Ching Chang

doi:10.1016/j.canlet.2018.06.029

HOTAIR is a REST-regulated lncRNA that promotes neuroendocrine differentiation in castration resistant prostate cancer

Cancer Lett. 2018 Oct 1:433:43-52. doi: 10.1016/j.canlet.2018.06.029. Epub 2018 Jun 23.

Authors

Affiliations

¹ Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
² Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan; Department of Urology, School of Medicine, Shu-Tien Urological Research Center, National Yang-Ming University, Taipei, Taiwan; Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan.
³ UC Davis Comprehensive Cancer Center, University of California, Davis, CA, 95616, USA.
⁴ Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan.
⁵ Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan.
⁶ Genome Research Center, National Yang-Ming University, Taipei, Taiwan.
⁷ Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan.
⁸ UC Davis Comprehensive Cancer Center, University of California, Davis, CA, 95616, USA; Department of Biochemistry and Molecular Medicine, University of California, Davis, CA, 95616, USA; Institute for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, 250 Wu-Xin Street, Taipei City, Taiwan; Division of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County, 35053, Taiwan.
⁹ Department of Pathology, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan.
¹⁰ Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan; Genome Research Center, National Yang-Ming University, Taipei, Taiwan; Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Cancer Progression Research Center, National Yang-Ming University, Taipei, Taiwan. Electronic address: pcchang@ym.edu.tw.

PMID: 29944905
DOI: 10.1016/j.canlet.2018.06.029

Abstract

Long non-coding RNAs (lncRNAs) are emerging as novel diagnostic markers of prostate cancer (PCa) and new determinants of castration-resistant PCa (CRPC), an aggressive and metastatic form of PCa. In addition to androgen receptor (AR) signaling, neuroendocrine differentiation (NED) is associated with CRPC. Recent reports demonstrate that the downregulation of repressor element-1 silencing transcription factor (REST) protein is a key step in NED of PCa cells. Here, we report HOTAIR as a novel REST-repressed lncRNA that is upregulated in NED PCa cells and in CRPC. HOTAIR overexpression is sufficient to induce, whereas knockdown of HOTAIR suppressed NED of PCa cells. Gene ontology (GO) analysis of differentially expressed genes under HOTAIR overexpression and in CRPC versus benign prostatic hyperplasia (BPH) suggests that HOTAIR may participate in PCa progression. Taken together, our results provide the first evidence of lncRNA HOTAIR as a driver for NED of PCa cells.

Keywords: Castration-resistant prostate cancer; HOTAIR; Long non-coding RNAs; Neuroendocrine differentiation; REST.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation
Cell Line, Tumor
Disease Progression
Gene Expression Regulation, Neoplastic
Humans
Male
Neurosecretory Systems / cytology*
Prostatic Neoplasms, Castration-Resistant / genetics*
Prostatic Neoplasms, Castration-Resistant / metabolism
RNA, Long Noncoding / genetics*
Repressor Proteins / genetics*
Repressor Proteins / metabolism
Sequence Analysis, RNA
Up-Regulation*

Substances

HOTAIR long untranslated RNA, human
RE1-silencing transcription factor
RNA, Long Noncoding
Repressor Proteins