TY - JOUR
T1 - Identification of AR-V7 downstream genes commonly targeted by AR/AR-V7 and specifically targeted by AR-V7 in castration resistant prostate cancer
AU - Sugiura, Masahiro
AU - Sato, Hiroaki
AU - Okabe, Atsushi
AU - Fukuyo, Masaki
AU - Mano, Yasunobu
AU - Shinohara, Ken ichi
AU - Rahmutulla, Bahityar
AU - Higuchi, Kosuke
AU - Maimaiti, Maihulan
AU - Kanesaka, Manato
AU - Imamura, Yusuke
AU - Furihata, Tomomi
AU - Sakamoto, Shinichi
AU - Komiya, Akira
AU - Anzai, Naohiko
AU - Kanai, Yoshikatsu
AU - Luo, Jun
AU - Ichikawa, Tomohiko
AU - Kaneda, Atsushi
N1 - Publisher Copyright:
© 2020
PY - 2021/1
Y1 - 2021/1
N2 - Primary prostate cancer (PC) progresses to castration-resistant PC (CRPC) under androgen deprivation therapy, by mechanisms e.g. expression of androgen receptor (AR) splice variant-7 (AR-V7). Here we conducted comprehensive epigenome and transcriptome analyses comparing LNCaP, primary PC cells, and LNCaP95, AR-V7-expressing CRPC cells derived from LNCaP. Of 399 AR-V7 target regions identified through ChIP-seq analysis, 377 could be commonly targeted by hormone-stimulated AR, and 22 were specifically targeted by AR-V7. Among genes neighboring to these AR-V7 target regions, 78 genes were highly expressed in LNCaP95, while AR-V7 knockdown led to significant repression of these genes and suppression of growth of LNCaP95. Of the 78 AR-V7 target genes, 74 were common AR/AR-V7 target genes and 4 were specific AR-V7 target genes; their most suppressed genes by AR-V7 knockdown were NUP210 and SLC3A2, respectively, and underwent subsequent analyses. NUP210 and SLC3A2 were significantly upregulated in clinical CRPC tissues, and their knockdown resulted in significant suppression of cellular growth of LNCaP95 through apoptosis and growth arrest. Collectively, AR-V7 contributes to CRPC proliferation by activating both common AR/AR-V7 target and specific AR-V7 target, e.g. NUP210 and SLC3A2.
AB - Primary prostate cancer (PC) progresses to castration-resistant PC (CRPC) under androgen deprivation therapy, by mechanisms e.g. expression of androgen receptor (AR) splice variant-7 (AR-V7). Here we conducted comprehensive epigenome and transcriptome analyses comparing LNCaP, primary PC cells, and LNCaP95, AR-V7-expressing CRPC cells derived from LNCaP. Of 399 AR-V7 target regions identified through ChIP-seq analysis, 377 could be commonly targeted by hormone-stimulated AR, and 22 were specifically targeted by AR-V7. Among genes neighboring to these AR-V7 target regions, 78 genes were highly expressed in LNCaP95, while AR-V7 knockdown led to significant repression of these genes and suppression of growth of LNCaP95. Of the 78 AR-V7 target genes, 74 were common AR/AR-V7 target genes and 4 were specific AR-V7 target genes; their most suppressed genes by AR-V7 knockdown were NUP210 and SLC3A2, respectively, and underwent subsequent analyses. NUP210 and SLC3A2 were significantly upregulated in clinical CRPC tissues, and their knockdown resulted in significant suppression of cellular growth of LNCaP95 through apoptosis and growth arrest. Collectively, AR-V7 contributes to CRPC proliferation by activating both common AR/AR-V7 target and specific AR-V7 target, e.g. NUP210 and SLC3A2.
KW - AR-V7
KW - Androgen receptor (AR)
KW - Castration-resistant prostate cancer (CRPC)
KW - NUP210
KW - SLC3A2
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UR - http://www.scopus.com/inward/citedby.url?scp=85092931933&partnerID=8YFLogxK
U2 - 10.1016/j.tranon.2020.100915
DO - 10.1016/j.tranon.2020.100915
M3 - Article
C2 - 33096335
AN - SCOPUS:85092931933
SN - 1944-7124
VL - 14
JO - Translational Oncology
JF - Translational Oncology
IS - 1
M1 - 100915
ER -