Mir-139 Regulates Autophagy in Prostate Cancer Cells Through Beclin-1 and mTOR Signaling Proteins.
Anticancer Res
; 40(12): 6649-6663, 2020 Dec.
Article
em En
| MEDLINE
| ID: mdl-33288559
ABSTRACT
BACKGROUND/AIM:
We previously identified a panel of five miRNAs (including miR-139) associated with biochemical recurrence and metastasis in prostate cancer patients. MATERIALS ANDMETHODS:
We examined miR-139 transfected PC3, DU145 and LNCaP cells by morphology as well as by cell-based assays, confocal microscopy and immunoblotting.RESULTS:
We found that treatment of prostate cancer cells with miR-139 resulted in phenotypic changes characteristic of autophagic cells. MiR-139 increased the autophagy-related conversion of the microtubule-associated protein light chain 3 (LC3-I to LC3-II) that was specifically inhibited by the miR-139 antagomir. The upregulation of LC3 II was further confirmed by confocal microscopy. miR-139 regulated activation of both mTOR and Beclin1 the two important autophagy-related molecules. We found that upon miR-139 treatment, the cargo adaptor protein p62 which is degraded during autophagy, accumulates.CONCLUSION:
These results suggest that miR-139 is inducing autophagic flux blockade leading to apoptosis in prostate cancer cells through the mTOR and Beclin-1 proteins.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Autofagia
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Transdução de Sinais
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MicroRNAs
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Serina-Treonina Quinases TOR
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Proteína Beclina-1
Tipo de estudo:
Prognostic_studies
Limite:
Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article