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微小RNA-492过表达通过靶向PAK7对骨肉瘤进展发挥抑制作用。

MicroRNA-492 overexpression exerts suppressive effects on the progression of osteosarcoma by targeting PAK7.

作者信息

Song Xuanhe, Xie Yaoping, Liu Yang, Shao Ming, Yang Weiliang

机构信息

Department of Orthopaedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

Department of Nuclear Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

出版信息

Int J Mol Med. 2017 Sep;40(3):891-897. doi: 10.3892/ijmm.2017.3046. Epub 2017 Jun 29.

Abstract

MicroRNAs (miRNAs or miRs), which are a class of non-coding RNAs, have emerged as effective modulators of various aspects of biological processes. Accumulating evidence has established significant associations between the dysregulation of miRs and tumorigenesis in various types of cancer. However, the role of miR‑492, particularly in osteosarcoma (OS) remains elusive. In present study, we demonstrated that miR‑492 functions as putative tumor suppressor miR in OS. The level of miR‑492 was frequently downregulated in both OS tissues and cell lines. Moreover, the ectopic overexpression of miR‑492 effectively inhibited the proliferation, migration and invasion of OS cell lines. Furthermore, transfection with a miR‑492 overexpression vector also strongly attenuated the growth of xenograft tumors in vivo. p21-activated kinase (PAK7) was identified as the putative target of miR‑492 in OS, and we further found a significantly inverse correlation between PAK7 and miR‑492 in OS specimens. Taken together, our study has unraveled a novel role for miR‑492 in OS and may help in establishing the rationale for more effective treatment strategies for OS via miR regulation.

摘要

微小RNA(miRNA或miR)是一类非编码RNA,已成为生物过程各个方面的有效调节因子。越来越多的证据表明,miR的失调与各种癌症的肿瘤发生之间存在显著关联。然而,miR-492的作用,尤其是在骨肉瘤(OS)中的作用仍不清楚。在本研究中,我们证明miR-492在OS中作为一种假定的肿瘤抑制性miR发挥作用。miR-492的水平在OS组织和细胞系中经常下调。此外,miR-492的异位过表达有效抑制了OS细胞系的增殖、迁移和侵袭。此外,用miR-492过表达载体转染也强烈减弱了体内异种移植肿瘤 的生长。p21激活激酶(PAK7)被确定为OS中miR-492的假定靶标,我们进一步发现OS标本中PAK7与miR-492之间存在显著的负相关。综上所述,我们的研究揭示了miR-492在OS中的新作用,并可能有助于通过miR调节为OS建立更有效的治疗策略的理论基础。

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