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DDX11-AS1 通过稳定 DDX11 促进骨肉瘤的进展。

DDX11-AS1 contributes to osteosarcoma progression via stabilizing DDX11.

机构信息

Shanghai Ocean University, No. 999 Hucheng Ring Road, Pudong New Area, 201306, Shanghai, China.

Department of Traumatic Orthopedics, Yantai Mountain Hospital, Yantai, 264000, China.

出版信息

Life Sci. 2020 Aug 1;254:117392. doi: 10.1016/j.lfs.2020.117392. Epub 2020 Jan 31.

DOI:10.1016/j.lfs.2020.117392
PMID:32014424
Abstract

Increasing evidence has uncovered that long noncoding RNAs (lncRNAs) play extremely important roles in numerous steps of gene regulation concerning the progression of tumors. Defined as a kind of lncRNA, DDX11-AS1 has been considered to be closely related to the tumorigenesis of malignancies. Nevertheless, the underlying regulatory role of it in osteosarcoma remains to be analyzed and elucidated. In this research, a dramatically upregulated expression of DDX11-AS1 was detected in osteosarcoma cells. Loss-of-function assays revealed that decreased expression of DDX11-AS1 impaired osteosarcoma cell proliferation, metastasis as well as epithelial-mesenchymal transition (EMT) process. Afterwards, molecular mechanism tests validated that DDX11-AS1 could sponge miR-873-5p to upregulate DDX11 expression in osteosarcoma. Additionally, functional tests delineated that upregulation of miR-873-5p inhibited cell proliferation, metastasis as well as EMT process in osteosarcoma progression. Further, DDX11-AS1 was verified to regulate the mRNA stability of DDX11 through binding with IGF2BP2 in osteosarcoma. Final rescue tests in vitro and in vivo further elucidated that DDX11 overexpression could reversed the DDX11-AS1 downregulation-mediated effect on osteosarcoma progression. To sum up, DDX11-AS1 contributes to osteosarcoma progression via stabilizing DDX11.

摘要

越来越多的证据表明,长非编码 RNA(lncRNA)在肿瘤进展过程中涉及的基因调控的多个步骤中发挥着极其重要的作用。DDX11-AS1 作为一种 lncRNA,被认为与恶性肿瘤的发生密切相关。然而,其在骨肉瘤中的潜在调节作用仍有待分析和阐明。在这项研究中,检测到骨肉瘤细胞中 DDX11-AS1 的表达显著上调。功能丧失实验表明,DDX11-AS1 表达降低会损害骨肉瘤细胞的增殖、转移以及上皮-间充质转化(EMT)过程。随后,分子机制测试验证了 DDX11-AS1 可以通过海绵吸附 miR-873-5p 来上调骨肉瘤中 DDX11 的表达。此外,功能测试表明,miR-873-5p 的上调抑制了骨肉瘤进展中的细胞增殖、转移和 EMT 过程。进一步研究表明,DDX11-AS1 通过与 IGF2BP2 结合来调节骨肉瘤中 DDX11 的 mRNA 稳定性。体外和体内的进一步挽救实验进一步阐明,DDX11 的过表达可以逆转 DDX11-AS1 下调对骨肉瘤进展的影响。总之,DDX11-AS1 通过稳定 DDX11 促进骨肉瘤的进展。

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