Exogenous Expression Of Mirna-3613-3p Causes Apaf1 Downregulation And Affects Several Proteins Involved In Apoptosis In Be(2)-C Human Neuroblastoma Cells

MicroRNAs (miRNAs) are a class of small non-coding RNAs involved in post-transcriptional gene regulation. Furthermore, dysregulation of miRNA expression is an important factor in the pathogenesis of neuroblastoma. Our previous study identified that overexpression of monocyte chemoattractant protein-induced protein 1 protein led to a significant downregulation of a novel miRNA molecule, miRNA-3613-3p. In the present study, the potential involvement of miRNA-3613 -3p in the cell biology of neuroblastoma was investigated. It was identified that the expression of miRNA-3613-3p varies among a range of human neuroblastoma cell lines. As the delineation of the functions of a miRNA requires the identification of its target genes, seven putative mRNAs that may be regulated by miRNA-3613-3p were selected. Furthermore, it was identified that overexpression of miRNA-3613-3p causes significant downregulation of several genes exhibiting tumor suppressive potential [encoding apoptotic protease-activating factor 1 (APAF1), Dicer, DNA fragmentation factor subunit 13, von Hippel-Lindau protein and neurofibromin 1] in BE(2)-C human neuroblastoma cells. APAF1 mRNA was the most significantly decreased transcript in the cells with miRNA-3613-3p overexpression. In accordance with the aforementioned results, the downregulation of cleaved caspase-9 and lack of activation of executive caspases in BE(2)-C cells following miRNA-3613-3p overexpression was observed. The results of the present study suggest a potential underlying molecular mechanism of apoptosis inhibition via APAF1 downregulation in human neuroblastoma BE(2)-C cells with miRNA-3613-3p overexpression.