miR-29b Mediates NF-κB Signaling in KRAS-Induced Non-Small Cell Lung Cancers.

Détails

ID Serval
serval:BIB_7D1D9B36E14C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
miR-29b Mediates NF-κB Signaling in KRAS-Induced Non-Small Cell Lung Cancers.
Périodique
Cancer research
Auteur(s)
Langsch S., Baumgartner U., Haemmig S., Schlup C., Schäfer S.C., Berezowska S., Rieger G., Dorn P., Tschan M.P., Vassella E.
ISSN
1538-7445 (Electronic)
ISSN-L
0008-5472
Statut éditorial
Publié
Date de publication
15/07/2016
Peer-reviewed
Oui
Volume
76
Numéro
14
Pages
4160-4169
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
A global understanding of miRNA function in EGFR signaling pathways may provide insights into improving the management of KRAS-mutant lung cancers, which remain relatively recalcitrant to treatment. To identify miRNAs implicated in EGFR signaling, we transduced bronchial epithelial BEAS-2B cells with retroviral vectors expressing KRAS(G12V) and monitored miRNA expression patterns by microarray analysis. Through this approach, we defined miR-29b as an important target for upregulation by mutant KRAS in non-small cell lung cancers. Cell biologic analyses showed that pharmacologic inhibition of EGFR or MEK was sufficient to reduce levels of miR-29b, while PI3K inhibition had no effect. In KRAS(G12V)-transduced BEAS-2B cells, introduction of anti-miR-29b constructs increased the sensitivity to apoptosis, arguing that miR-29b mediated apoptotic resistance conferred by mutant KRAS. Mechanistic investigations traced this effect to the ability of miR-29b to target TNFAIP3/A20, a negative regulator of NF-κB signaling. Accordingly, overexpression of an miR-29b-refractory isoform of TNFAIP3 restored NF-κB and extrinsic apoptosis, confirming that TNFAIP3 is a functionally relevant target of miR-29b. We also noted that miR-29b could confer sensitivity to intrinsic apoptosis triggered by exposure to cisplatin, a drug used widely in lung cancer treatment. Thus, miR-29b expression may tilt cells from extrinsic to intrinsic mechanisms of apoptosis. Overall, our results reveal a complexity in cancer for miR-29b, which can act as either an oncogene or tumor suppressor gene depending on signaling context. Cancer Res; 76(14); 4160-9. ©2016 AACR.
Mots-clé
Apoptosis, Carcinoma, Non-Small-Cell Lung/pathology, Cell Line, Tumor, ErbB Receptors/genetics, ErbB Receptors/physiology, Humans, Lung Neoplasms/pathology, MAP Kinase Signaling System, MicroRNAs/physiology, Mutation, NF-kappa B/physiology, Proto-Oncogene Proteins p21(ras)/genetics, Signal Transduction/physiology, Tumor Necrosis Factor alpha-Induced Protein 3/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/06/2020 11:01
Dernière modification de la notice
30/06/2020 5:26
Données d'usage