Conclusions
MicroRNA-375 regulates invadopodia maturation and function potentially by suppressing the expression and secretion of proteases.
Objective
To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. Design: For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of cortactin. Human protease arrays were used for the detection of the secreted proteases. Quantitative real time-polymerase chain reaction measurements were used to evaluate the messenger RNA (mRNA) expression of the commonly regulated proteases.
Results
Increased miR-375 expression in HNSCC cells suppresses extracellular matrix degradation and reduces the number of mature invadopodia. Higher miR-375 expression does not reduce cellular levels of selected invadopodia-associated proteins, nor is tyrosine phosphorylation of cortactin altered. However, HNSCC cells with higher miR-375 expression had significant reductions in the mRNA expression levels and secreted levels of specific proteases. Conclusions: MicroRNA-375 regulates invadopodia maturation and function potentially by suppressing the expression and secretion of proteases.