RNA Interference Targeting Aurora Kinase A Suppresses Tumor Growth In Human Laryngeal Cancer Cells

RNA interference targeting Aurora kinase A suppresses tumor growth in human laryngeal cancer cellsObjective:To investigate the expression of Aurora kinase A (AURKA) and its association with clinicopathological features in human laryngeal squamous cell carcinoma (LSCC). To investigate the effects of knockdown of AURKA on laryngeal cancer HEp-2 cells both in vitro and in vivo.Methods:The expression of AURKA mRNA and protein were studied using reverse transcription-PCR and western blot in LSCC tissues and corresponding normal epithelium respectively. In addition, the correlation between AURKA expression and clinicopathologic characteristics was analyzed in LSCC patients.A plasmid containing short hairpin (sh)RNA against AURKA was constructed and transfected into HEp-2. Measurements included the CCK-8 assay for viability and proliferation, flow cytometry for apoptosis and effects on the mitotic checkpoint, a trans-well assay for migration, immunofluorescence for assessment of genomic instability, and western blotting for protein expression.Results:The expression of AURKA mRNA was significantly upregulated in laryngeal tumor tissue compared with that in normal tissue, and over expression of Aurora-A was found in 64.0%(16 of 25) of the patients by western blotting. Upregulation of Aurora-A mRNA was significantly correlated with regional lymph node metastasis and clinical stage?/?. Overexpression of AURKA was significantly associated with lymph node metastasis.AURKA knockdown inhibited proliferation, migration, and colony formation in vitro and tumorigenicity in vivo. The knockdown induced the accumulation of cells in G2-M phase and eventual apoptosis. Knockdown of AURKA caused delayed entry into mitosis after treatment with nocodazole, reduced chromosomal instability, and decreased expression of focal adhesion kinase (FAK), phosphorylated FAK, and matrix metalloproteinase-2 (MMP-2), key regulators in cell adhesion and invasion.Conclusion:AURKA expression is elevated in human LSCC and associated with regional lymph node metastasis and late clinical stage. Knockdown of AURKA inhibits the growth and invasiveness of LSCC cells both in vitro and in vivo. These effects may partially result from the reduced expression of FAK and MMP-2. Knockdown of AURKA expression may represent a promising therapeutic strategy for the treatment of LSCC.