PDCD4 Is an Androgen-Repressed Tumor Suppressor that Regulates Prostate Cancer Growth and Castration Resistance.
Androgens
/ metabolism
Animals
Apoptosis
/ genetics
Apoptosis Regulatory Proteins
/ biosynthesis
Cell Growth Processes
/ genetics
Cell Line, Tumor
Genes, Tumor Suppressor
HEK293 Cells
Heterografts
Humans
Male
Mice
Mice, Nude
MicroRNAs
/ genetics
Neoplasm Grading
Prostatic Neoplasms, Castration-Resistant
/ genetics
RNA-Binding Proteins
/ biosynthesis
Transfection
Journal
Molecular cancer research : MCR
ISSN: 1557-3125
Titre abrégé: Mol Cancer Res
Pays: United States
ID NLM: 101150042
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
07
08
2018
revised:
09
10
2018
accepted:
21
11
2018
pubmed:
7
12
2018
medline:
28
1
2020
entrez:
7
12
2018
Statut:
ppublish
Résumé
Androgen receptor (AR) transcriptional activity contributes to prostate cancer development and castration resistance. The growth and survival pathways driven by AR remain incompletely defined. Here, we found PDCD4 to be a new target of AR signaling and a potent regulator of prostate cancer cell growth, survival, and castration resistance. The 3' untranslated region of PDCD4 is directly targeted by the androgen-induced miRNA, miR-21. Androgen treatment suppressed PDCD4 expression in a dose responsive and miR-21-dependent manner. Correspondingly, AR inhibition dose-responsively induced PDCD4 expression. Using data from prostate cancer tissue samples in The Cancer Genome Atlas (TCGA), we found a significant and inverse correlation between miR-21 and PDCD4 mRNA and protein levels. Higher Gleason grade tumors exhibited significantly higher levels of miR-21 and significantly lower levels of PDCD4 mRNA and protein. PDCD4 knockdown enhanced androgen-dependent cell proliferation and cell-cycle progression, inhibited apoptosis, and was sufficient to drive androgen-independent growth. On the other hand, PDCD4 overexpression inhibited miR-21-mediated growth and androgen independence. The stable knockdown of PDCD4 in androgen-dependent prostate cancer cells enhanced subcutaneous tumor take rate
Identifiants
pubmed: 30518628
pii: 1541-7786.MCR-18-0837
doi: 10.1158/1541-7786.MCR-18-0837
pmc: PMC6359980
mid: NIHMS1515327
doi:
Substances chimiques
Androgens
0
Apoptosis Regulatory Proteins
0
MIRN21 microRNA, human
0
MicroRNAs
0
PDCD4 protein, human
0
RNA-Binding Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
618-627Subventions
Organisme : NCI NIH HHS
ID : P30 CA006973
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA058236
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA143299
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA200859
Pays : United States
Informations de copyright
©2018 American Association for Cancer Research.
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