Cancer-associated fibroblast exosomes promote prostate cancer metastasis through miR-500a-3p/FBXW7/HSF1 axis under hypoxic microenvironment.
Cancer Gene Ther
; 31(5): 698-709, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38351137
ABSTRACT
Metastasis is the main cause of deaths in prostate cancer (PCa). However, the exact mechanisms underlying PCa metastasis are not fully understood. In this study, we discovered pronounced hypoxia in primary lesions of metastatic PCa(mPCa). The exosomes secreted by cancer-associated fibroblasts (CAFs) under hypoxic conditions significantly enhance PCa metastasis both in vitro and in vivo. Through miRNA sequencing and reverse transcription quantitative PCR (RT-qPCR), we found that hypoxia elevated miR-500a-3p levels in CAFs exosomes. Subsequent RT-qPCR, western blotting, and dual luciferase reporter assays identified F-box and WD repeat domain-containing 7(FBXW7) as a target of miR-500a-3p. In addition, immunohistochemistry revealed that FBXW7 expression decreased with the progression of PCa, while heat shock transcription factor 1(HSF1) expression increased. Introducing an FBXW7 plasmid into PCa cells reduced their metastatic potential and significantly lowered HSF1 expression. These findings suggest that CAFs exosomes drive PCa metastasis via the miR-500a-3p/FBXW7/HSF1 axis in a hypoxic microenvironment. Targeting either hypoxia or exosomal miR-500a-3p could be a promising strategy for PCa management.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prostatic Neoplasms
/
MicroRNAs
/
Exosomes
/
Tumor Microenvironment
/
Cancer-Associated Fibroblasts
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F-Box-WD Repeat-Containing Protein 7
/
Neoplasm Metastasis
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Cancer Gene Ther
Journal subject:
GENETICA MEDICA
/
NEOPLASIAS
/
TERAPEUTICA
Year:
2024
Type:
Article
Affiliation country:
China