MiR-409-3p Inhibits Cell Proliferation and Invasion of Osteosarcoma by Targeting Zinc-Finger E-Box-Binding Homeobox-1

• Main Authors: Liang Wu, Yiming Zhang, Zhongyue Huang, Huijie Gu, Kaifeng Zhou, Xiaofan Yin, Jun Xu
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-02-01
• Series: Frontiers in Pharmacology
• Subjects: osteosarcoma; microRNA-409; molecular mechanism; zinc-finger E-box-binding homeobox-1; invasion
• Online Access: https://www.frontiersin.org/article/10.3389/fphar.2019.00137/full

Osteosarcoma (OS) is the most common bone cancer worldwide. There is evidence that microRNA-409 (miR-409-3p) is involved in tumorigenesis and cancer progression, however, its possible role in OS requires clarification. In the present study, we evaluated the expression level, clinical significance, and mode of action of miR-409-3p in OS. The miR-409-3p levels were diminished in the OS cells and tissues compared with associated adjacent non-tumor tissues and a non-cancer osteoplastic cell line. Low miR-409-3p expression levels were associated with clinical stage and distant metastasis in patients with OS. Resumption of miR-409-3p expression attenuated OS cell proliferation and invasion. Additionally, based on informatics analyses, we predicted that zinc-finger E-box-binding homeobox-1 (ZEB1) is a possible target of miR-409-3p. This hypothesis was confirmed using luciferase reporter assays, reverse transcription-quantitative real-time polymerase chain reaction, and Western blot analyses. The findings of the current study indicated that ZEB1 was up-regulated in the OS tissues and cell lines, and that this up-regulation was inversely proportional to miR-409-3p expression levels. Furthermore, down-regulation of ZEB1 decreased OS cell invasion and proliferation, illustrating that the tumor suppressive role of miR-409-3p in OS cells may be exerted via negative regulation of ZEB1. Taken together, our observations highlight the potential role of miR-409-3p as a tumor suppressor in OS partially through down-regulation of ZEB1 and suggest that miR-409-3p has potential applications in OS treatment.