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微小 RNA-660 的下调通过直接靶向叉头框 O1 抑制骨肉瘤细胞的增殖和侵袭。

Downregulation of microRNA‑660 inhibits cell proliferation and invasion in osteosarcoma by directly targeting forkhead box O1.

机构信息

Department of Neurosurgery, Fujian Sanbo Funeng Brain Hospital, Fuzhou, Fujian 350001, P.R. China.

Department of Oncology, Dongying People's Hospital, Dongying, Shandong 257000, P.R. China.

出版信息

Mol Med Rep. 2018 Aug;18(2):2433-2440. doi: 10.3892/mmr.2018.9165. Epub 2018 Jun 14.

Abstract

The abnormal expression of microRNAs (miRNAs/miRs) has been observed in osteosarcoma (OS), and these differently expressed miRNAs contribute to the occurrence and development of OS by regulating various biological behaviours. Therefore, a comprehensive understanding of the detailed roles of aberrantly expressed miRNAs in OS progression may be favourable to the identification of promising therapeutic strategies for the treatment of patients with this malignancy. The present study demonstrated that miR‑660‑5p (miR‑660) expression was significantly upregulated in OS tissues and cell lines compared with that in normal adjacent tissues and normal human osteoblast hFOB1.19, respectively. miR‑660 downregulation led to a significant decrease in the proliferation and invasion of OS cells. Forkhead box O1 (FOXO1) was predicted as a potential target of miR‑660. The subsequent luciferase reporter assay indicated that miR‑660 directly binds to the 3'‑untranslated region of FOXO1. Furthermore, miR‑660 inhibition increased the FOXO1 expression in OS cells at mRNA and protein levels. Moreover, FOXO1 was downregulated in OS tissues and this downregulation was negatively correlated with miR‑660 levels. Besides, rescue experiments demonstrated that FOXO1 knockdown abolished the effects of miR‑660 knockdown on OS cell proliferation and invasion. These results suggest that miR‑660 may serve oncogenic roles in OS by directly targeting FOXO1. Targeting miR‑660 may be an effective candidate for the treatment of patients with OS.

摘要

微小 RNA(miRNAs/miRs)的异常表达已在骨肉瘤(OS)中观察到,这些差异表达的 miRNAs 通过调节各种生物学行为促进 OS 的发生和发展。因此,全面了解异常表达的 miRNAs 在 OS 进展中的详细作用可能有利于确定治疗这种恶性肿瘤患者的有前途的治疗策略。本研究表明,miR-660-5p(miR-660)在 OS 组织和细胞系中的表达明显高于正常相邻组织和正常人成骨细胞 hFOB1.19。miR-660 的下调导致 OS 细胞的增殖和侵袭能力显著降低。叉头框 O1(FOXO1)被预测为 miR-660 的潜在靶标。随后的荧光素酶报告基因实验表明,miR-660 直接结合 FOXO1 的 3'-UTR。此外,miR-660 抑制在 OS 细胞中增加 FOXO1 的 mRNA 和蛋白水平表达。此外,OS 组织中下调 FOXO1,且这种下调与 miR-660 水平呈负相关。此外,挽救实验表明,FOXO1 敲低消除了 miR-660 敲低对 OS 细胞增殖和侵袭的影响。这些结果表明,miR-660 可能通过直接靶向 FOXO1 在 OS 中发挥致癌作用。靶向 miR-660 可能是治疗 OS 患者的有效候选物。

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