miR-9 modulates and predicts the response to radiotherapy and EGFR inhibition in HNSCC.
EGFR inhibitors
HNSCC
KLF5
Sp1
radiotherapy
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
07 07 2021
07 07 2021
Historique:
revised:
28
04
2021
received:
04
06
2020
accepted:
07
05
2021
pubmed:
2
6
2021
medline:
26
10
2021
entrez:
1
6
2021
Statut:
ppublish
Résumé
Radiotherapy (RT) plus the anti-EGFR monoclonal antibody Cetuximab (CTX) is an effective combination therapy for a subset of head and neck squamous cell carcinoma (HNSCC) patients. However, predictive markers of efficacy are missing, resulting in many patients treated with disappointing results and unnecessary toxicities. Here, we report that activation of EGFR upregulates miR-9 expression, which sustains the aggressiveness of HNSCC cells and protects from RT-induced cell death. Mechanistically, by targeting KLF5, miR-9 regulates the expression of the transcription factor Sp1 that, in turn, stimulates tumor growth and confers resistance to RT+CTX in vitro and in vivo. Intriguingly, high miR-9 levels have no effect on the sensitivity of HNSCC cells to cisplatin. In primary HNSCC, miR-9 expression correlated with Sp1 mRNA levels and high miR-9 expression predicted poor prognosis in patients treated with RT+CTX. Overall, we have discovered a new signaling axis linking EGFR activation to Sp1 expression that dictates the response to combination treatments in HNSCC. We propose that miR-9 may represent a valuable biomarker to select which HNSCC patients might benefit from RT+CTX therapy.
Identifiants
pubmed: 34062049
doi: 10.15252/emmm.202012872
pmc: PMC8261495
doi:
Substances chimiques
MicroRNAs
0
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Cetuximab
PQX0D8J21J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12872Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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