Objective: Head and neck squamous cell carcinoma (HNSCC) represents as a common malignancy with increasing incidence in the worldwide. The fact of its poor survival rate urgently requires developing efficient predictive biomarkers for clinical use. MicroRNAs (miRNAs) recently represent as a novel direction for early diagnosis and prognosis prediction in HNSCC therapy. In this study, we comprehensively investigated the function and putative target of miRNA-451 in vitro.
Methods: The expression of miRNA-451 was detected in HNSCC tissues and cell lines by real-time PCR. Forced expression or inhibition of miRNA-451 was done by transient transfection of mimics or inhibitor of miRNA-451 into indicated cells, respectively. Cell proliferation was evaluated by cell counting and crystal staining. Afterwards, we perform western blot to verify the expression of the miRNA-451 predicted target, c-myc, after miRNA-451 was overexpressed.
Results: We showed that miRNA-451 was downregulated in paired HNSCC tissues as well as in cell lines. And overexpression of miRNA-451 in cells with low endogenous expression of miRNA-451 accelerated proliferation. To the contrast, knockdown of miRNA-451 in cells with high levels of miRNA-451 significantly reduced cell growth rate. Furthermore, we used bioinformatics and cellular methods to predict and prove that c-myc was targeted by miRNA-451, since forced expression of miRNA-451 leaded to decreased c-myc protein expression in HNSCC cells.
Conclusion: Our findings identify miRNA-451 as a potential biomarker and suggest a key role of miRNA-451-c-myc pathway in HNSCC cell transformation, which could represent a novel therapeutic strategy in HNSCC treatment.