TRIM44, a crucial target of miR-410, functions as a potential oncogene in osteosarcoma

Onco Targets Ther. 2018 Jun 21:11:3637-3647. doi: 10.2147/OTT.S163163. eCollection 2018.

Abstract

Purpose: Mounting evidence highlights the essential role of TRIM44 in tumor initiation and malignant progression in several cancers; however, the function of TRIM44 in osteosarcoma (OS) remains unknown. In this study, we aim to investigate the role of TRIM44 and reveal its regulation by deregulated miRNAs in OS.

Materials and methods: The expression profiles of TRIM44 were examined by immunohistochemistry, Western blotting, and qRT-PCR. The biological functions of TRIM44 were investigated through siRNA-mediated knockdown experiments. The regulation of TRIM44 by miR-410 was confirmed by Western blotting, dual luciferase reporter assays, and rescue experiments.

Results: TRIM44 was upregulated in OS tissues and cell lines, and its overexpression was positively correlated with TNM stage, metastasis, and recurrence. Knockdown of TRIM44 in OS cells suppressed cell proliferation, migration, invasion, and epithelial-mesenchymal transition. In addition, we identified TRIM44 as a novel target gene of miR-410 and miR-410 was remarkably downregulated in OS. Moreover, overexpression of miR-410 suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition of OS cells by directly targeting TRIM44 expression. Furthermore, reintroduction of TRIM44 partially reversed miR-410-induced inhibitory effects on OS cells.

Conclusion: Collectively, our findings indicate that the miR-410/TRIM44 link is critical in the control of OS progression.

Keywords: TRIM44; invasion; miR-410; osteosarcoma; proliferation.