MiR-338-3p Inhibits Cell Growth, Invasion, and EMT Process in Neuroblastoma Through Targeting MMP-2

This study aimed to explore the regulatory mechanisms of miR-338-3p and matrix metalloproteinase-2 (MMP-2) in neuroblastoma. Putative target interaction regions of miR-338-3p on MMP-2 were predicted by miRcode and miRbase bioinformatics tools. Relative expression of miRNA-338-3p and MMP-2 in neuroblastoma tissues and GI-LI-N and SK-N-SH cells was determined by reverse transcription polymerase chain reaction experiment. Furthermore, the cell proliferation was determined by Cell Counting Kit-8 assay, the cell apoptosis rate was analyzed by flow cytometry assay, and the cell invasion was evaluated by transwell assay. miR-338-3p expression was downregulated, whereas MMP-2 expression was upregulated in metastasis tissue site compared to that in primary tissue site in total. Furthermore, miR-338-3p overexpression suppressed proliferation, invasion, and epithelial-mesenchymal transition (EMT) of neuroblastoma cells but promoted apoptosis, and the knockdown of MMP-2 triggered similar effects. Furthermore, MMP-2 was directly targeted by miR-338-3p, and overexpression of MMP-2 rescued the inhibitory effects of miR-338-3p on human neuroblastoma cell progression. Collectively, these data demonstrated that miR-338-3p could suppress cell growth, invasion, and EMT pathway and induce apoptosis in neuroblastoma cells by targeting MMP-2. MiR-338-3p sponged MMP-2 to regulate the PI3K/AKT pathway in human neuroblastoma cells.