MicroRNA-154 functions as a tumor suppressor in osteosarcoma by targeting Wnt5a.

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that are involved in tumor initiation and development by suppressing target gene expression. miRNA-154 has been shown to be important in tumorigenesis in many types of cancers. However, its role in osteosarcoma (OS) remains unknown. In the present study, we focused on the roles and mechanisms of miR‑154 in OS development. The results of quantitative RT‑PCR showed that miR‑154 expression was decreased in primary OS tumor samples and cell lines compared to levels in the matched adjacent normal tissues and human normal osteoblast cells (NHOst). Restoration of expression in U2OS cells inhibited cell proliferation, colony formation, migration and invasion, as well as induced cell cycle arrest at the G1 stage. Bioinformatic prediction suggested that Wnt5a is a target gene of miR‑154. It was further verified that Wnt5a is a target gene of miR‑150 in OS cells using luciferase assay, mRNA and protein expression analysis. Wnt5a was upregulated in OS cell lines and primary tumor samples, and its mRNA expression level was negatively correlated with the miR‑154 level in the OS tissues. Restored expression of Wnt5a weakened miR‑154‑mediated suppression of tumor progression. Taken together, these findings suggest that miR‑154 functions as a tumor suppressor in OS by partially suppressing Wnt5a expression.