A miR-210-3p regulon that controls the Warburg effect by modulating HIF-1α and p53 activity in triple-negative breast cancer.
Animals
Cell Line, Tumor
Female
Heterografts
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
/ genetics
MCF-7 Cells
Male
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs
/ genetics
Regulon
Transfection
Triple Negative Breast Neoplasms
/ genetics
Tumor Suppressor Protein p53
/ genetics
Warburg Effect, Oncologic
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
09 09 2020
09 09 2020
Historique:
received:
28
04
2020
accepted:
27
08
2020
revised:
18
08
2020
entrez:
10
9
2020
pubmed:
11
9
2020
medline:
28
4
2021
Statut:
epublish
Résumé
Reprogrammed energy metabolism, especially the Warburg effect (aerobic glycolysis), is an emerging hallmark of cancer. Different from other breast cancer subtypes, triple-negative breast cancer (TNBC) exhibits high metabolic remodeling, increased aggressiveness and lack of targeted therapies. MicroRNAs (miRNA) are essential to TNBC malignant phenotypes. However, little is known about the contribution of miRNA to aerobic glycolysis in TNBC. Through an integrated analysis and functional verification, we reported that several miRNAs significantly correlates to the Warburg effect in TNBC, including miR-210-3p, miR-105-5p, and miR-767-5p. Ectopic expression of miR-210-3p enhanced glucose uptake, lactate production, extracellular acidification rate, colony formation ability, and reduced serum starvation-induced cell apoptosis. Moreover, GPD1L and CYGB were identified as two functional mediators of miR-210-3p in TNBC. Mechanistically, miR-210-3p targeted GPD1L to maintain HIF-1α stabilization and suppressed p53 activity via CYGB. Ultimately, miR-210-3p facilitated aerobic glycolysis through modulating the downstream glycolytic genes of HIF-1α and p53. Taken together, our results decipher miRNAs that regulate aerobic glycolysis and uncover that miR-210-3p specifically contributes to the Warburg effect in TNBC.
Identifiants
pubmed: 32908121
doi: 10.1038/s41419-020-02952-6
pii: 10.1038/s41419-020-02952-6
pmc: PMC7481213
doi:
Substances chimiques
HIF1A protein, human
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
MIRN210 microRNA, human
0
MicroRNAs
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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