Inhibition of miR-328-3p Impairs Cancer Stem Cell Function and Prevents Metastasis in Ovarian Cancer.
Animals
Apoptosis
Biomarkers, Tumor
/ genetics
Cell Movement
Cell Proliferation
Extracellular Signal-Regulated MAP Kinases
/ genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Inbred NOD
Mice, SCID
MicroRNAs
/ genetics
Neoplasm Metastasis
Neoplastic Stem Cells
/ metabolism
Ovarian Neoplasms
/ genetics
Prognosis
Survival Rate
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
01 05 2019
01 05 2019
Historique:
received:
21
11
2018
revised:
31
01
2019
accepted:
12
03
2019
pubmed:
22
3
2019
medline:
8
2
2020
entrez:
22
3
2019
Statut:
ppublish
Résumé
Cancer stem cells (CSC) play a central role in cancer metastasis and development of drug resistance. miRNA are important in regulating CSC properties and are considered potential therapeutic targets. Here we report that miR-328-3p (miR-328) is significantly upregulated in ovarian CSC. High expression of miR-328 maintained CSC properties by directly targeting DNA damage binding protein 2, which has been shown previously to inhibit ovarian CSC. Reduced activity of ERK signaling in ovarian CSC, mainly due to a low level of reactive oxygen species, contributed to the enhanced expression of miR-328 and maintenance of CSC. Inhibition of miR-328 in mouse orthotopic ovarian xenografts impeded tumor growth and prevented tumor metastasis. In summary, our findings provide a novel mechanism underlying maintenance of the CSC population in ovarian cancer and suggest that targeted inhibition of miR-328 could be exploited for the eradication of CSC and aversion of tumor metastasis in ovarian cancer. SIGNIFICANCE: These findings present inhibition of miR-328 as a novel strategy for efficient elimination of CSC to prevent tumor metastasis and recurrence in patients with epithelial ovarian cancer.
Identifiants
pubmed: 30894370
pii: 0008-5472.CAN-18-3668
doi: 10.1158/0008-5472.CAN-18-3668
pmc: PMC6777340
mid: NIHMS1052490
doi:
Substances chimiques
Biomarkers, Tumor
0
MIRN328 microRNA, human
0
MicroRNAs
0
Extracellular Signal-Regulated MAP Kinases
EC 2.7.11.24
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2314-2326Subventions
Organisme : NCI NIH HHS
ID : P30 CA016058
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA211175
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
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