Long non-coding RNA MANCR is a target of BET bromodomain protein BRD4 and plays a critical role in cellular migration and invasion abilities of prostate cancer

Biochem Biophys Res Commun. 2020 May 21;526(1):128-134. doi: 10.1016/j.bbrc.2020.03.043. Epub 2020 Mar 18.

Abstract

Androgen receptor (AR)-negative castration-resistant prostate cancer (CRPC) is highly aggressive and is resistant to most of the current therapies. Bromodomain and extra terminal domain (BET) protein BRD4 binds to super-enhancers (SEs) that drive high expression of oncogenes in many cancers. A BET inhibitor, JQ1, has been found to suppress the malignant phenotypes of prostate cancer cells, however, the target genes of JQ1 remain largely unknown. Here we show that SE-associated genes specific for AR-negative CRPC PC3 cells include genes involved in migration and invasion, and that JQ1 impairs migration and invasion of PC3 cells. We identified a long non-coding RNA, MANCR, which was markedly down-regulated by JQ1, and found that BRD4 binds to the MANCR locus. MANCR knockdown led to a significant decrease in migration and invasion of PC3 cells. Furthermore, RNA sequencing analysis revealed that expression of the genes involved in migration and invasion was altered by MANCR knockdown. In summary, our data demonstrate that MANCR plays a critical role in migration and invasion of PC3 cells.

Keywords: BET protein inhibitor; Epithelial-mesenchymal transition; MANCR; Prostate cancer; Super-enhancer; lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azepines / pharmacology
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement* / drug effects
  • Cell Movement* / genetics
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Enhancer Elements, Genetic / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Neoplasm Invasiveness
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism*
  • Transcription Factors / metabolism*
  • Triazoles / pharmacology

Substances

  • (+)-JQ1 compound
  • Azepines
  • BRD4 protein, human
  • Cell Cycle Proteins
  • RNA, Untranslated
  • Transcription Factors
  • Triazoles