Abstract
MicroRNAs (miRNAs) are small, single-stranded, non-coding RNA molecules involved in cancer initiation and progression. The present study aimed to determine the effect of miRNA-30d (miR-30d) on the growth, malignant phenotype, and apoptosis of Ewing's sarcoma (ES) SK-ES-1 cells, and to elucidate the underlying molecular mechanism and signaling pathway involved. Cell proliferation, invasion, migration, morphological changes, cell cycle distribution and apoptosis were investigated. Furthermore, the expression of matrix metalloproteinase (MMP)-2, MMP-9, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3 and poly (ADP-ribose) polymerase (PARP) were examined, as was the activity of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/Akt pathways. It was found that the overexpression of miR-30d repressed the proliferation, migration and invasion, and promoted morphological changes, S-phase arrest and apoptosis of SK-ES-1 cells. Additionally, it was observed that increased miR-30d levels inhibited the expression of MMP-2 and MMP-9, and inhibited the activity of the MEK/ERK and PI3K/Akt pathways, but elevated the ratio of Bax/Bcl-2 and the cleavage of caspase-3 and PARP. Taken together, the results demonstrated that miR-30d suppressed the biological progression of SK-ES-1 cells by targeting MMP-2 and MMP9, the Bax/Bcl-2 and caspase-3 cascade, and the MEK/ERK and PI3K/Akt signaling pathways. Therefore, miR-30d is a promising target in the treatment of ES. However, further investigations are urgently required to investigate the underlying molecular mechanisms of the effects of miR-30d on ES for a comprehensive understanding of the tumorigenesis and progression of this cancer.