MicroRNA‑873 targets HOXA9 to inhibit the aggressive phenotype of osteosarcoma by deactivating the Wnt/β‑catenin pathway.

Several microRNAs (miRNAs or miRs) that regulate a variety of cancer‑related events are dysregulated in osteosarcoma (OS). An exploration of the specific roles of miRNAs in OS is crucial for the identification of suitable therapeutic targets. Previous studies have shown that miR‑873 plays tumor suppressive or oncogenic roles in different types of cancer. However, whether miR‑873 is implicated in OS carcinogenesis and cancer progression remains poorly understood. In the present study, we demonstrated that the miR‑873 levels were decreased in OS tissues and cell lines. The decreased expression of miR‑873 was related to tumor size, clinical stage and distant metastasis in patients with OS. The introduction of miR‑873 significantly inhibited tumor cell proliferation, migration and invasion in vitro, promoted apoptosis in vitro and restricted tumor growth in vivo. Furthermore, homeobox A9 (HOXA9) was validated as a direct target gene of miR‑873 in OS cells. HOXA9 was markedly expressed in OS tissues, and its upregulation inversely correlated with the miR‑873 levels. Moreover, HOXA9 silencing produced similar effects as observed with miR‑873 overexpression in OS cells. Consistently, the exogenous expression of HOXA9 partially reversed the suppression of the aggressive phenotype induced by miR‑873 overexpression in OS cells. Notably, miR‑873 was able to deactivate the Wnt/β‑catenin pathway in OS cells by regulating HOXA9, both in vitro and in vivo. On the whole, the present study demonstrates that miR‑873 suppresses the development of OS by directly targeting HOXA9 and inhibiting the Wnt/β‑catenin pathway, and suggests that miR‑873 may prove to be useful as a diagnostic biomarker of OS, as well as in the development of novel therapies.