Androgen receptor suppresses prostate cancer metastasis but promotes bladder cancer metastasis via differentially altering miRNA525-5p/SLPI-mediated vasculogenic mimicry formation

Copyright © 2019 Elsevier B.V. All rights reserved..

Early studies suggest that the androgen receptor (AR) may play differential roles in influencing prostate cancer (PCa) and bladder cancer (BCa) metastasis, but the underlying mechanisms remain unclear. Here, we found that the AR might function via differentially altering vasculogenic mimicry (VM) formation to either decrease PCa metastasis or increase BCa metastasis. Mechanism dissection showed that the AR could differentially alter the expression of the VM marker SLPI through miR-525-5p to regulate SLPI; moreover, it could either increase miR-525-5p transcription in PCa or decrease it in BCa via binding to different androgen-response-elements (AREs) located at different positions in the miR-525 precursor promoter. Further, results from liquid chromatography-mass spectrometry (LC-MS) showed that the co-factors of AR in PCa and BCa are NFIX and HDAC2, respectively. Together, these results provide the first detailed mechanism of how the AR can differentially alter PCa and BCa metastasis; thus, targeting the newly identified AR-miR-525-5p-SLPI axis may help suppress metastasis.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:473

Enthalten in:

Cancer letters - 473(2020) vom: 31. März, Seite 118-129

Sprache:

Englisch

Beteiligte Personen:

Yang, Zhao [VerfasserIn]
Chen, Jiaqi [VerfasserIn]
Xie, Hongjun [VerfasserIn]
Liu, Tianjie [VerfasserIn]
Chen, Yule [VerfasserIn]
Ma, Zhenkun [VerfasserIn]
Pei, Xinqi [VerfasserIn]
Yang, Wenjie [VerfasserIn]
Li, Lei [VerfasserIn]

Links:

Volltext

Themen:

2010-15-3
93T0T9GKNU
AR protein, human
Androgen Antagonists
Androgen receptor
Antineoplastic Agents
Benzamides
Bladder cancer
EC 3.5.1.98
Enzalutamide
HDAC2 protein, human
Histone Deacetylase 2
Journal Article
MIRN525 microRNA, human
MiRNA-525-5p
MicroRNAs
NFI Transcription Factors
NFIX protein, human
Nitriles
Phenylthiohydantoin
Prostate cancer
RNA, Small Interfering
Receptors, Androgen
Research Support, Non-U.S. Gov't
SLPI protein, human
Secretory Leukocyte Peptidase Inhibitor
Vasculogenic mimicry

Anmerkungen:

Date Completed 05.10.2020

Date Revised 04.12.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.canlet.2019.12.018

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM304445258