Send to

Choose Destination
Oncotarget. 2017 Jul 11;8(34):57174-57186. doi: 10.18632/oncotarget.19170. eCollection 2017 Aug 22.

MiR-223-3p inhibits angiogenesis and promotes resistance to cetuximab in head and neck squamous cell carcinoma.

Author information

Université Côte d'Azur, INSERM, CNRS, IRCAN, Nice, France.
Head and Neck University Institute, Nice, France.
FHU OncoAge, Nice, France.
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.
Hospital-Related Biobank (BB-0033-00025), Pasteur Hospital, Nice, France.
Contributed equally


MicroRNAs (miRs) participate in tumor growth and dissemination by regulating expression of various target genes. MiR-223-3p is suspected of being involved in head and neck squamous cell carcinoma (HNSCC) growth although its precise role has not been elucidated. In this study, we showed that miR-223-3p is present in biopsies of HNSCC patients and that its presence is correlated with high neutrophil infiltrate. We found that overexpression of miR-223-3p slightly increased proliferation of the CAL27 squamous carcinoma cell line both in vitro and in vivo. Moreover, miR-223-3p induced CAL27 apoptosis in an orthotopic xenograft mouse model, counteracting the proliferative effect and resulting in no impact on overall tumor growth. We analyzed the effect of miR-223-3p overexpression on signaling pathways and showed that it induced pERK2, pAKT and AKT, consistent with an increase in cell proliferation. In addition, we found that miR-223-3p reduced the STAT3 level correlating with increased cell apoptosis and inhibited vasculature formation. In HNSCC tissues, miR-223-3p expression was inversely correlated to CD31, highlighting the relationship between miR-223 and vessel formation. Finally, we studied the effect of miR-223-3p on response to selected anticancer agents and showed that cells expressing miR-223-3p are more resistant to drugs, notably cetuximab. In conclusion, our study is the first to show the antiangiogenic properties of miR-223-3p in HNSCC patients and to question whether expression levels of miR-223-3p can be evaluated as an indicator of eligibility for non-treatment of HNSCC patients with cetuximab.


MiRs; anticancer agents; inflammation; neutrophils; tumors

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center