Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan City, Hubei Province, China.
Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan City, Hubei Province, China.
Int J Biol Macromol. 2019 Jul 15;133:137-147. doi: 10.1016/j.ijbiomac.2019.04.016. Epub 2019 Apr 4.
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.
微小 RNA（miRNAs）是骨肉瘤（OS）发生和发展的关键调节因子。基于我们之前的基因芯片数据，我们发现 miR-335 在 OS 组织中的表达相对正常组织下调。在此基础上，我们进一步发现 miR-335 在 OS 细胞系中相对于成骨细胞系 hFOB 1.19 下调。进一步的功能实验发现，miR-335 的上调抑制了 OS 细胞在体外的增殖、侵袭和迁移以及体内的肿瘤生长和肺转移。此外，miR-335 的上调导致总共 750 个 mRNAs 的表达降低，并且发现 SNIP1 是 miR-335 的直接靶标。SNIP1 表达的恢复减弱了 miR-335 对 OS 细胞的抑制作用。此外，miR-335 在体外和体内抑制了 SNIP1、MMP-2 和 MMP-7 的 mRNA 和蛋白表达。miR-335 还在体外和体内抑制了 c-Myc 和 NFκb p65 的表达。总之，我们的数据表明 miR-335 在 OS 的肿瘤发生和转移中起重要作用，可能成为 OS 治疗的治疗靶点。
