Open AccessMicro RNA ‐9 inhibits growth and invasion of head and neck cancer cells and is a predictive biomarker of response to plerixafor, an inhibitor of its target CXCR 4
Author(s) -
Hersi Hersi Mohamed,
Raulf Nina,
Gaken Joop,
Folarin Najeem'deen,
Tavassoli Mahvash
Publication year - 2018
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12352
Subject(s) - biomarker , plerixafor , cancer research , head and neck cancer , rna , cancer , medicine , chemistry , biology , receptor , cxcr4 , gene , biochemistry , chemokine
Head and neck squamous cell carcinomas ( HNSCC ) are associated with poor morbidity and mortality. Current treatment strategies are highly toxic and do not benefit over 50% of patients. There is therefore a crucial need for predictive and/or prognostic biomarkers to allow treatment stratification for individual patients. One class of biomarkers that has recently gained importance are micro RNA (mi RNA ). Mi RNA are small, noncoding molecules which regulate gene expression post‐transcriptionally. We performed mi RNA expression profiling of a cohort of head and neck tumours with known clinical outcomes. The results showed miR‐9 to be significantly downregulated in patients with poor treatment outcome, indicating its role as a potential biomarker in HNSCC . Overexpression of miR‐9 in HNSCC cell lines significantly decreased cellular proliferation and inhibited colony formation in soft agar. Conversely, miR‐9 knockdown significantly increased both these features. Importantly, endogenous CXCR 4 expression levels, a known target of miR‐9, inversely correlated with miR‐9 expression in a panel of HNSCC cell lines tested. Induced overexpression of CXCR 4 in low expressing cells increased proliferation, colony formation and cell cycle progression. Moreover, CXCR 4‐specific ligand, CXCL 12, enhanced cellular proliferation, migration, colony formation and invasion in CXCR 4‐overexpressing and similarly in miR‐9 knockdown cells. CXCR 4‐specific inhibitor plerixafor abrogated the oncogenic phenotype of CXCR 4 overexpression as well as miR‐9 knockdown. Our data demonstrate a clear role for miR‐9 as a tumour suppressor micro RNA in HNSCC , and its role seems to be mediated through CXCR 4 suppression. MiR‐9 knockdown, similar to CXCR 4 overexpression, significantly promoted aggressive HNSCC tumour cell characteristics. Our results suggest CXCR 4‐specific inhibitor plerixafor as a potential therapeutic agent, and miR‐9 as a possible predictive biomarker of treatment response in HNSCC .