LKB1 Down-Modulation by miR-17 Identifies Patients With NSCLC Having Worse Prognosis Eligible for Energy-Stress-Based Treatments.
LKB1
Lung cancer
Metformin
miR-17
Journal
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
ISSN: 1556-1380
Titre abrégé: J Thorac Oncol
Pays: United States
ID NLM: 101274235
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
30
06
2020
revised:
19
03
2021
accepted:
04
04
2021
pubmed:
23
4
2021
medline:
10
8
2021
entrez:
22
4
2021
Statut:
ppublish
Résumé
Preclinical models recently unveiled the vulnerability of LKB1/KRAS comutated NSCLC to metabolic stress-based treatments. Because miR-17 is a potential epigenetic regulator of LKB1, we hypothesized that wild-type LKB1 (LKB1 We took advantage of NSCLC cell lines with different combinations of KRAS mutation and LKB1 deletion and of patient-derived xenografts (PDXs) with high (LKB1 We identified miR-17 as an epigenetic regulator of LKB1 in NSCLC and confirmed targeting of miR-17 to LKB1 3' untranslated region by luciferase reporter assay. We found that miR-17 overexpression functionally impairs the LKB1/AMPK pathway. Metformin treatment prompted apoptosis on miR-17 overexpression only in LKB1 We identified miR-17 as a mediator of LKB1 expression in NSCLC tumors. This study proposes a miR-17 expression score potentially exploitable to discriminate LKB1
Identifiants
pubmed: 33887464
pii: S1556-0864(21)02115-8
doi: 10.1016/j.jtho.2021.04.005
pii:
doi:
Substances chimiques
MIRN17 microRNA, human
0
MicroRNAs
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1298-1311Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 International Association for the Study of Lung Cancer. All rights reserved.