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MicroRNA-340 通过直接靶向 ROCK1 抑制骨肉瘤肿瘤生长和转移。

MicroRNA-340 suppresses osteosarcoma tumor growth and metastasis by directly targeting ROCK1.

机构信息

Department of Orthopaedic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, China.

出版信息

Biochem Biophys Res Commun. 2013 Aug 9;437(4):653-8. doi: 10.1016/j.bbrc.2013.07.033. Epub 2013 Jul 18.

Abstract

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.

摘要

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。

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