Mir-139 Regulates Autophagy in Prostate Cancer Cells Through Beclin-1 and mTOR Signaling Proteins.
Apoptosis
/ genetics
Autophagy
/ genetics
Beclin-1
/ metabolism
Cell Line, Tumor
Cell Shape
/ genetics
Down-Regulation
/ genetics
Gene Expression Regulation, Neoplastic
Humans
MAP Kinase Signaling System
Male
MicroRNAs
/ metabolism
Phosphatidylinositol 3-Kinases
/ metabolism
Prostatic Neoplasms
/ genetics
Proto-Oncogene Proteins c-akt
/ metabolism
Signal Transduction
TOR Serine-Threonine Kinases
/ metabolism
Up-Regulation
/ genetics
Beclin-1
LC3B-II
SQSTM1
apoptosis
autophagy
chloroquine
mTOR
miR-139
prostate cancer
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
07
10
2020
revised:
19
10
2020
accepted:
23
10
2020
entrez:
8
12
2020
pubmed:
9
12
2020
medline:
17
12
2020
Statut:
ppublish
Résumé
We previously identified a panel of five miRNAs (including miR-139) associated with biochemical recurrence and metastasis in prostate cancer patients. We examined miR-139 transfected PC3, DU145 and LNCaP cells by morphology as well as by cell-based assays, confocal microscopy and immunoblotting. 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. 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.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
We previously identified a panel of five miRNAs (including miR-139) associated with biochemical recurrence and metastasis in prostate cancer patients.
MATERIALS AND METHODS
METHODS
We examined miR-139 transfected PC3, DU145 and LNCaP cells by morphology as well as by cell-based assays, confocal microscopy and immunoblotting.
RESULTS
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
CONCLUSIONS
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.
Identifiants
pubmed: 33288559
pii: 40/12/6649
doi: 10.21873/anticanres.14689
doi:
Substances chimiques
Beclin-1
0
MIRN139 microRNA, human
0
MicroRNAs
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6649-6663Informations de copyright
Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.