Department of Orthopedic, The People's Hospital of Cixi, No. 999 East Nanerhuan Road, Hushan Street, Cixi, 315300, People's Republic of China.
Hum Cell. 2019 Jul;32(3):390-396. doi: 10.1007/s13577-019-00256-2. Epub 2019 May 11.
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.
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。