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Downregulated microRNA (miR)-124 is common in numerous types of cancer, including non-small cell lung cancer (NSCLC). A previous study by the authors demonstrated that LIM-homeobox domain 2 (LHX2) was upregulated and promoted cell growth in NSCLC. However, whether LHX2 affects the migratory and invasive abilities of NSCLC cells and the association of LHX2 with miR-124 remains unclear. The present study revealed that miR-124 expression was frequently decreased in human NSCLC cells and tissues and negatively correlated with LHX2 expression, which was increased in NSCLC cells and tissues. Furthermore, the transfection of miR-124 mimic significantly inhibited endogenous expression of LHX2 mRNA and protein in A549 and H1299 cells, and miR-124 inhibitor promoted LHX2 expression. Of note, overexpression of miR-124 in A549 and H1299 cells attenuated cellular migratory and invasive abilities, and this was observed in LHX2-silenced A549 and H1299 cells. Knockdown of miR-124 augmented the migratory and invasive abilities in A549 and H1299 cells. The 3'-untranslated region of LHX2 transcript has also been identified to be a putative target of miR-124. Taken together, the results revealed that miR-124 may inhibit migration and invasion by repressing LHX2 expression in NSCLC cells. The findings of the present study suggested that overexpression of miR-124 or silencing of LHX2 may provide a therapeutic strategy for advanced NSCLC. [ABSTRACT FROM AUTHOR]