RESUMEN
BACKGROUND: Neuroblastoma (NB) comprises about 8-10% of pediatric cancers, and microRNA (miR)-338 downregulation has been implicated in NB. However, the underlying molecular mechanism remains largely unclear. The main goal of this study is to probe the regulatory role of miR-338 and the upstream and downstream biomolecules involved in NB. METHODS: The differentially expressed miRNAs were screened by analyzing the NB gene expression microarray GSE121513 from the GEO database, and the differences in expression of the screened miRNAs were verified in clinically collected NB tissues versus dorsal root ganglions. Subsequently, the relationship between the miR-338 expression and NB cell growth was validated in vitro and in vivo, and the upstream and downstream regulatory mechanisms of miR-338 were further analyzed by bioinformatics. Functional rescue experiments were used to verify their effects on NB cell growth. RESULTS: miR-338 expressed poorly in NB tissues, and overexpression of miR-338 significantly inhibited NB cell growth in vitro and in vivo. The prediction results showed that miR-338 could target KIF1A, and miR-338 expression was negatively correlated with the expression of KIF1A. We further found that miR-338 was transcriptionally regulated by the transcription factor KLF5. Overexpression of KLF5 or KIF1A significantly attenuated the inhibitory effect of miR-338 mimic on NB cell growth. Finally, miR-338 blocked the Hedgehog signaling pathway by inhibiting the expression of KIF1A. CONCLUSION: Overexpression of KLF5 reduced expression of miR-338, which in turn increased the expression of KIF1A and activated the Hedgehog signaling pathway, leading to the progression of NB.