MiR-9 modulates and predicts the response to radiotherapy and EGFR-inhibition in HNSCC

ABSTRACT: 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 exp

SUBMITTER: Dr. Francesca Citron 

PROVIDER: S-SCDT-EMM-2020-12872 | biostudies-other |

REPOSITORIES: biostudies-other