Overexpression of miR-335 inhibits the migration and invasion of osteosarcoma by targeting SNIP1

Abstract

MicroRNAs (miRNAs) are key regulators in the development and progression of osteosarcoma (OS). Based on our previous microarray data, we found that miR-335 expression was downregulated in OS tissue relative to normal tissue. Herein, we further found that miR-335 was downregulated in OS cell lines relative to the osteoblastic cell line hFOB 1.19. Further functional experiments found that upregulation of miR-335 suppressed the proliferation, invasion and migration of OS cells in vitro and tumor growth and lung metastasis in vivo. In addition, the expression of a total of 750 mRNAs was decreased upon the upregulation of miR-335, and SNIP1 was found to be the direct target of miR-335. Restoration of SNIP1 expression attenuated the suppressive effect of miR-335 on OS cells. Additionally, miR-335 suppressed the mRNA and protein expression of SNIP1, MMP-2, and MMP-7 in vitro and in vivo. MiR-335 also suppressed c-Myc and NFκb p65 in vitro and in vivo. In conclusion, our data suggest that miR-335 plays a significant role in the tumorigenesis and metastasis of OS and may serve as a therapeutic target for OS treatment.

Keywords: Invasion; Migration; Osteosarcoma; Smad nuclear interacting protein 1; miR-335.