MicroRNA-377 exerts a potent suppressive role in osteosarcoma through the involvement of the histone acetyltransferase 1-mediated Wnt axis.

Abstract

It has been demonstrated that microRNAs (miRNAs) may contribute to tumorigenesis and tumor growth in osteosarcoma (OS), which is a primary malignant tumor of bone frequently diagnosed in adolescents and young people. The purpose of our investigation was to evaluate the functional relevance of miR-377 in OS and to investigate whether the mechanism was related to the histone acetyltransferase 1 (HAT1)-mediated Wnt signaling pathway. By screening differentially expressed genes in microarray GSE47572, HAT1 was found to be a candidate gene of interest. Besides, the regulatory miRNA (miR-377) of HAT1 was also selected. The interaction among miR-377, HAT1, and the Wnt signaling pathway was evaluated. In addition, the miR-377 expression was altered in OS cells (U-2OS and SOSP-9607) to assess the in vitro cell apoptosis and the in vivo tumor growth. OS tissues presented elevated HAT1 expression and decreased miR-377 expression. A putative miR-377 binding site in HAT1 3'-UTR HAT1 was verified. Cells with miR-377 overexpression or HAT1 silencing were observed to exhibit reduced HAT1 expression and promoted apoptosis, accompanied by blockade of Wnt signaling. Moreover, the in vivo experiment revealed that miR-377 overexpression or HAT1 silencing inhibited tumor growth and reduced tumor size in nude mice. Taken together, our results conclude that miR-377 may promote OS cell apoptosis through inactivation of the HAT1-mediated Wnt signaling pathway, highlighting the potential therapeutic effect of miR-377 on OS treatment.