TY - JOUR
T1 - 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
AU - Nagasawa, Masayuki
AU - Tomimatsu, Kosuke
AU - Terada, Koji
AU - Kondo, Kenta
AU - Miyazaki, Kazuko
AU - Miyazaki, Masaki
AU - Motooka, Daisuke
AU - Okuzaki, Daisuke
AU - Yoshida, Tetsuya
AU - Kageyama, Susumu
AU - Kawamoto, Hiroshi
AU - Kawauchi, Akihiro
AU - Agata, Yasutoshi
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/5/21
Y1 - 2020/5/21
N2 - 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.
AB - 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.
KW - BET protein inhibitor
KW - Epithelial-mesenchymal transition
KW - MANCR
KW - Prostate cancer
KW - Super-enhancer
KW - lncRNA
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UR - http://www.scopus.com/inward/citedby.url?scp=85081948338&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2020.03.043
DO - 10.1016/j.bbrc.2020.03.043
M3 - Article
C2 - 32199616
AN - SCOPUS:85081948338
SN - 0006-291X
VL - 526
SP - 128
EP - 134
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -
