PMID- 34099592
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211101
IS  - 1976-9148 (Print)
IS  - 2005-4483 (Electronic)
IS  - 1976-9148 (Linking)
VI  - 29
IP  - 6
DP  - 2021 Nov 1
TI  - AR-mTOR-SRF Axis Regulates HMMR Expression in Human Prostate Cancer Cells.
PG  - 667-677
LID - 10.4062/biomolther.2021.040 [doi]
AB  - The elevated expression of the hyaluronan-mediated motility receptor (HMMR) is 
      known to be highly associated with tumor progression in prostate cancer, but the 
      molecular mechanisms underlying the regulation of HMMR expression remain unclear. 
      Here, we report that mammalian target of rapamycin (mTOR) is a key regulator of 
      HMMR expression, for which its kinase activity is required. Pharmacological 
      inhibitors of mTOR, such as rapamycin and Torin2, markedly suppressed the mRNA 
      level as well as the protein level of HMMR in LNCaP and PC-3 cells. Our data 
      demonstrate that such regulation occurs at the transcription level. HMMR promoter 
      reporter assays revealed that the transcription factor SRF is responsible for the 
      mTOR-mediated transcriptional regulation of HMMR gene. Consistently, the 
      suppression of HMMR expression by Torin2 was noticeably reversed by the 
      overexpression of SRF. Moreover, our findings suggest that the SRF binding sites 
      responsible for the transcriptional regulation of HMMR through the mTOR-SRF axis 
      are located in HMMR promoter sequences carrying the first intron, downstream of 
      the translational start site. Furthermore, the upregulation of HMMR by DHT was 
      abolished by stimulation with rapamycin, prior to DHT treatment, suggesting that 
      mTOR activity is required for the induction of HMMR expression by androgen. 
      Collectively, our study provides new mechanistic insights into the role of 
      mTOR/SRF/AR signaling in HMMR regulation in prostate cancer cells.
FAU - Sun, You
AU  - Sun Y
AD  - Department of Herbal Resources, Professional Graduate School of Oriental 
      Medicine, Wonkwang University, Iksan 54538, Republic of Korea.
FAU - Li, Zewu
AU  - Li Z
AD  - Department of Herbal Resources, Professional Graduate School of Oriental 
      Medicine, Wonkwang University, Iksan 54538, Republic of Korea.
FAU - Song, Kyung
AU  - Song K
AD  - Department of Herbal Resources, Professional Graduate School of Oriental 
      Medicine, Wonkwang University, Iksan 54538, Republic of Korea.
AD  - Department of Pharmacy, College of Pharmacy, Wonkwang University, Iksan 54538, 
      Republic of Korea.
AD  - Institute of Pharmaceutical Research and Development, Wonkwang University, Iksan 
      54538, Republic of Korea.
AD  - Integrated Omics Institute, Wonkwang University, Iksan 54538, Republic of Korea.
LA  - eng
PT  - Journal Article
PL  - Korea (South)
TA  - Biomol Ther (Seoul)
JT  - Biomolecules & therapeutics
JID - 101472832
PMC - PMC8551732
OTO - NOTNLM
OT  - Androgen receptor
OT  - HMMR
OT  - Prostate cancer
OT  - SRF
OT  - Transcriptional regulation
OT  - mTOR
EDAT- 2021/06/09 06:00
MHDA- 2021/06/09 06:01
PMCR- 2021/06/08
CRDT- 2021/06/08 05:58
PHST- 2021/02/27 00:00 [received]
PHST- 2021/04/24 00:00 [revised]
PHST- 2021/05/16 00:00 [accepted]
PHST- 2021/06/09 06:00 [pubmed]
PHST- 2021/06/09 06:01 [medline]
PHST- 2021/06/08 05:58 [entrez]
PHST- 2021/06/08 00:00 [pmc-release]
AID - biomolther.2021.040 [pii]
AID - bt-29-6-667 [pii]
AID - 10.4062/biomolther.2021.040 [doi]
PST - ppublish
SO  - Biomol Ther (Seoul). 2021 Nov 1;29(6):667-677. doi: 10.4062/biomolther.2021.040.