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

• Published in: Biochemical and biophysical research communications Vol. 526; no. 1; pp. 128 - 134
• Main Authors: Nagasawa, Masayuki, Tomimatsu, Kosuke, Terada, Koji, Kondo, Kenta, Miyazaki, Kazuko, Miyazaki, Masaki, Motooka, Daisuke, Okuzaki, Daisuke, Yoshida, Tetsuya, Kageyama, Susumu, Kawamoto, Hiroshi, Kawauchi, Akihiro, Agata, Yasutoshi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.05.2020
• Subjects: androgen receptors; BET protein inhibitor; cell movement; Epithelial-mesenchymal transition; lncRNA; loci; MANCR; non-coding RNA; oncogenes; Prostate cancer; prostatic neoplasms; Super-enhancer; Epithelial-mesenchymal transition; Super-enhancer; MANCR; lncRNA; BET protein inhibitor; Prostate cancer
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2020.03.043

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. •Super-enhancer associated genes in PC3 cells are enriched in EMT pathways.•Migratory and invasive abilities of PC3 cells are reduced by BET protein inhibitor.•The lncRNA MANCR is markedly down-regulated by BET protein inhibitor in PC3 cells.•MANCR positively regulates cell migration and invasion in prostate cancer cell lines.