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miR-376a 通过靶向 FBXO11 抑制骨肉瘤的增殖和侵袭。

miR-376a inhibits the proliferation and invasion of osteosarcoma by targeting FBXO11.

机构信息

Department of Orthopedic, The People's Hospital of Cixi, No. 999 East Nanerhuan Road, Hushan Street, Cixi, 315300, People's Republic of China.

出版信息

Hum Cell. 2019 Jul;32(3):390-396. doi: 10.1007/s13577-019-00256-2. Epub 2019 May 11.

Abstract

Dysregulation of microRNAs (miRNAs) is frequently found in the tumorigenesis of osteosarcoma (OS). miR-376a was found to play tumor suppressive roles in human cancers. However, the role of miR-376a in OS remains unclear. The expression of miR-376a was analyzed by quantitative real-time PCR (qRT-PCR) in OS cell lines. Cell proliferation assay, cell invasion assay, and cell apoptosis assay were performed to detect the biological function of miR-376a after synthetic miRNA transfection. The target of miR-376a was predicted by TargetScan and miRDB, and further validated by luciferase activity reporter assay and western blot. miR-376a expression was revealed to be decreased in OS cell lines. In vitro experiments showed that overexpression of miR-376a inhibits OS cell proliferation and invasion but promotes apoptosis. Luciferase activity reporter assay and western blot assay showed F-box protein 11 (FBXO11) was a direct target of miR-376a. Furthermore, FBXO11 mediated the role of miR-376a on the proliferation, invasion, and apoptosis of OS cells. Collectively, these results revealed miR-376a functions as a tumor suppressor by targeting FBXO11 in OS. It may be developed as a therapeutic target for OS patients.

摘要

miRNAs(miRNAs)的失调在骨肉瘤(OS)的肿瘤发生中经常被发现。miR-376a 被发现在人类癌症中发挥肿瘤抑制作用。然而,miR-376a 在 OS 中的作用仍不清楚。通过定量实时 PCR(qRT-PCR)分析 OS 细胞系中 miR-376a 的表达。合成 miRNA 转染后进行细胞增殖试验、细胞侵袭试验和细胞凋亡试验,以检测 miR-376a 的生物学功能。通过 TargetScan 和 miRDB 预测 miR-376a 的靶标,并通过荧光素酶活性报告基因测定和 Western blot 进一步验证。结果显示 miR-376a 在 OS 细胞系中表达降低。体外实验表明,miR-376a 的过表达抑制 OS 细胞的增殖和侵袭,但促进凋亡。荧光素酶活性报告基因测定和 Western blot 分析表明 F-box 蛋白 11(FBXO11)是 miR-376a 的直接靶标。此外,FBXO11 介导了 miR-376a 对 OS 细胞增殖、侵袭和凋亡的作用。综上所述,这些结果表明 miR-376a 通过靶向 OS 中的 FBXO11 发挥肿瘤抑制作用。它可能被开发为 OS 患者的治疗靶点。

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