Breast Cancer Stem Cells-derived Extracellular Vesicles Affect PPARG Expression by Delivering MicroRNA-197 in Breast Cancer Cells.
Clin Breast Cancer
; 22(5): 478-490, 2022 07.
Article
em En
| MEDLINE
| ID: mdl-35279406
ABSTRACT
BACKGROUND:
Breast cancer (BC) is the most frequently diagnosed cancer in women, and over 90% of BC-related deaths are associated with metastasis. The effects of BC stem cells-derived extracellular vesicles (BCSCs-EVs) have been implicated in cancer control. This work aims to probe to the relevance of BCSCs-EVs to liver metastases of BC cells and the molecules involved.METHODS:
First, EVs were extracted from BCSCs for MDA-MB-231 and SUM149PT cell co-culture. The effects of BCSCs-EVs on the proliferation of BC cells in vitro and in vivo as well as liver metastasis were evaluated. Subsequently, we analyzed differentially expressed microRNAs (miRNAs) after BCSCs-EVs by microRNA microarray and had them verified by RT-qPCR. Bioinformatics analysis was conducted to analyze target mRNAs of miR-197. The binding relationship of miR-197 to PPARG mRNA was examined. Finally, MDA-MB-231 and SUM149PT cells co-cultured with BCSCs-EVs were treated with miR-197 inhibitor or a PPARG-specific agonist.RESULTS:
BCSCs-EVs promoted the growth of MDA-MB-231 and SUM149PT cells in vitro and in vivo as well as liver metastasis. BCSCs-EVs increased the expression of miR-197 in MDA-MB-231 and SUM149PT cells, and miR-197 could target PPARG mRNA. BCSCs-EVs treatment inhibited the mRNA and protein expression of PPARG in cells, thereby activating epithelial-mesenchymal transition (EMT). Knockdown of miR-197 or activation of PPARG in BCSCs-EVs-treated cells significantly counteracted the promoting effect of BCSCs-EVs on BC cell growth and metastasis.CONCLUSION:
BCSCs-EVs facilitated EMT of BC cells by delivering miR-197 to BC cells and inhibiting PPARG expression, thereby promoting growth and metastasis of BC cells.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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MicroRNAs
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Vesículas Extracelulares
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Neoplasias Hepáticas
Limite:
Female
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Humans
Idioma:
En
Revista:
Clin Breast Cancer
Ano de publicação:
2022
Tipo de documento:
Article