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miR-214-3p 和鸢尾素/FNDC5 对骨肉瘤细胞生物学行为的影响。

The Effects of MiR-214-3p and Irisin/FNDC5 on the Biological Behavior of Osteosarcoma Cells.

机构信息

Department of Orthopedics, Yantaishan Hospital, Yantai, China.

Department of Orthopedics, The Second Affiliated Hospital of Shandong First Medical University, Taian, China.

出版信息

Cancer Biother Radiopharm. 2020 Mar;35(2):92-100. doi: 10.1089/cbr.2019.2933. Epub 2020 Feb 19.

Abstract

Irisin/fibronectin type III domain-containing protein 5 (FNDC5) has important effects on breast cancer and liver cancer, however, its role in osteosarcoma is poorly understood. This study explored the effects of irisin/FNDC5 in osteosarcoma cells, aiming to provide a direction for treating osteosarcoma. The expression levels of irisin/FNDC5 in serums and tissues of osteosarcoma patients and the expression characteristics of FNDC5 in osteosarcoma cell lines were measured. The effects of irisin, at different concentrations (0, 25, 50, 100, and 200 ng/mL), and FNDC5 on the viability, migration, and invasion of U2OS cells were analyzed. The target gene regulating FNDC5 was predicted, and its effects on irisin/FNDC5 and osteosarcoma cells were further explored. The authors found that irisin/FNDC5 was significantly downregulated in the serums and tissues of osteosarcoma patients, and FNDC5 was also lowly expressed in osteosarcoma cell lines, especially in U2OS cells. Irisin/FNDC5 could not only inhibit the viability of U2OS cell in a concentration- and time-dependent manner but could also suppress cell migration and invasion. Furthermore, miR-214-3p inhibited the expression of irisin/FNDC5, and promoted the migration, invasion, and epithelial/mesenchymal transition (EMT) of U2OS cell through targeting FNDC5. Irisin/FNDC5 could inhibit the viability, migration, invasion, and EMT of osteosarcoma cells, and miR-214-3p could target FNDC5 to release its antitumor effects. Thus, irisin/FNDC5 and miR-214-3p might become a new direction for the treatment of osteosarcoma patients in the future.

摘要

鸢尾素/纤连蛋白 III 型结构域蛋白 5(FNDC5)对乳腺癌和肝癌有重要影响,但其在骨肉瘤中的作用尚不清楚。本研究探讨了鸢尾素/FNDC5 在骨肉瘤细胞中的作用,旨在为骨肉瘤的治疗提供方向。 测量了骨肉瘤患者血清和组织中鸢尾素/FNDC5 的表达水平,以及骨肉瘤细胞系中 FNDC5 的表达特征。分析了不同浓度(0、25、50、100 和 200ng/mL)的鸢尾素和 FNDC5 对 U2OS 细胞活力、迁移和侵袭的影响。预测了调节 FNDC5 的靶基因,并进一步探讨了其对鸢尾素/FNDC5 和骨肉瘤细胞的影响。 作者发现,鸢尾素/FNDC5 在骨肉瘤患者的血清和组织中明显下调,FNDC5 在骨肉瘤细胞系中也低表达,尤其是在 U2OS 细胞中。鸢尾素/FNDC5 不仅可以浓度和时间依赖性地抑制 U2OS 细胞的活力,还可以抑制细胞迁移和侵袭。此外,miR-214-3p 通过靶向 FNDC5 抑制鸢尾素/FNDC5 的表达,促进 U2OS 细胞的迁移、侵袭和上皮/间充质转化(EMT)。 鸢尾素/FNDC5 可抑制骨肉瘤细胞的活力、迁移、侵袭和 EMT,miR-214-3p 可通过靶向 FNDC5 释放其抗肿瘤作用。因此,鸢尾素/FNDC5 和 miR-214-3p 可能成为未来骨肉瘤患者治疗的一个新方向。

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