MiR-18a upregulation enhances autophagy in triple negative cancer cells via inhibiting mTOR signaling pathway.
Eur Rev Med Pharmacol Sci
; 20(11): 2194-200, 2016 06.
Article
em En
| MEDLINE
| ID: mdl-27338042
ABSTRACT
OBJECTIVE:
We investigated the involvement of miR-18a upregulation in autophagy regulation and paclitaxel (PTX) resistance in triple negative breast cancer (TNBC) cells. MATERIALS ANDMETHODS:
PTX resistant MDA-MMB-231/PTX cells were generated using an intermittent, stepwise method. MiR-18a expression was assessed using qRT-PCR. The level of autophagy was assessed by Western blot analysis of LC3B expression and observation of LC3-GFP puncta formation under a fluorescence microscope. The effect of miR-18a mediated autophagy on PTX sensitivity was assessed by measuring IC50 and PTX induced cell apoptosis.RESULTS:
MDA-MB-231/PTX cells had both higher miR-18a expression and basal autophagy than MDA-MB-231 cells. Enforced miR-18a overexpression directly led to increased autophagy in MDA-MB-231 cells, the effect of which was similar to that of rapamycin, a mTOR signaling inhibitor. Following Western blot analysis showed that miR-18a overexpression decreased the expression of p-mTOR and p-p70S6. Therefore, we infer that miR-18a increases autophagy level in MDA-MB-231 cells via inhibiting mTOR signaling pathway. Both drug sensitivity assay and flow cytometry analysis confirmed that the effect of miR-18a on increasing IC50 and decreasing PTX induced apoptosis in MDA-MB-231 cells could largely be abrogated by treatment with bafilomycin A1 (Baf. A1).CONCLUSIONS:
MiR-18a upregulation results in enhanced autophagy via inhibiting mTOR signaling pathway in TNBC cells, which is a mechanism contributing to paclitaxel resistance.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Regulação para Cima
/
MicroRNAs
/
Neoplasias de Mama Triplo Negativas
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article