Department of Orthopaedic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, China.
Biochem Biophys Res Commun. 2013 Aug 9;437(4):653-8. doi: 10.1016/j.bbrc.2013.07.033. Epub 2013 Jul 18.
MicroRNAs (miRNAs) play key roles in cancer development and progression. In the present study, we investigated the role of miR-340 in the progression and metastasis of osteosarcoma (OS). Our results showed that miR-340 was frequently downregulated in OS tumors and cell lines. Overexpression of miR-340 in OS cell lines significantly inhibited cell proliferation, migration, and invasion in vitro, and tumor growth and metastasis in a xenograft mouse model. ROCK1 was identified as a target of miR-340, and ectopic expression of miR-340 downregulated ROCK1 by direct binding to its 3' untranslated region. siRNA-mediated silencing of ROCK1 phenocopied the effects of miR-340 overexpression, whereas restoration of ROCK1 in miR-340-overexpressing OS cells reversed the suppressive effects of miR-340. Together, these findings indicate that miR-340 acts as a tumor suppressor and its downregulation in tumor tissues may contribute to the progression and metastasis of OS through a mechanism involving ROCK1, suggesting miR-340 as a potential new diagnostic and therapeutic target for the treatment of OS.
微小 RNA(miRNAs)在癌症的发生和发展中发挥着关键作用。在本研究中,我们研究了 miR-340 在骨肉瘤(OS)进展和转移中的作用。我们的结果表明,miR-340 在 OS 肿瘤和细胞系中经常下调。在 OS 细胞系中过表达 miR-340 显著抑制体外细胞增殖、迁移和侵袭,以及异种移植小鼠模型中的肿瘤生长和转移。ROCK1 被鉴定为 miR-340 的靶标,并且 miR-340 通过直接与其 3'非翻译区结合而下调 ROCK1 的表达。ROCK1 的 siRNA 介导的沉默模拟了 miR-340 过表达的效果,而在 miR-340 过表达的 OS 细胞中恢复 ROCK1 则逆转了 miR-340 的抑制作用。总之,这些发现表明 miR-340 作为一种肿瘤抑制因子,其在肿瘤组织中的下调可能通过涉及 ROCK1 的机制促进 OS 的进展和转移,提示 miR-340 作为治疗 OS 的潜在新的诊断和治疗靶点。