MicroRNA-221 Promotes Cell Proliferation and Inhibits Apoptosis in Osteosarcoma Cells by Directly Targeting FBXW11 and Regulating Wnt Signaling

被引:18
|
作者
Zhang, Qingzhu [1 ]
Yin, Xuelian [2 ]
Zhang, Yi [3 ]
机构
[1] Chengde Med Univ, Dept Orthoped, Affiliated Hosp, Chengde, Peoples R China
[2] Chengde Med Univ, Dept Stomatol, Affiliated Hosp, Chengde, Peoples R China
[3] Chengde Med Univ, Dept Orthoped Trauma, Affiliated Hosp, Chengde 067000, Hebei, Peoples R China
关键词
microRNAs; miR-221; FBXW11; Osteosarcoma cells; Cancer progression;
D O I
10.1016/j.arcmed.2020.10.017
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background and objectives. MicroRNAs play a crucial role in the progression of various cancers, and microRNA-221 (miR-221) has been observed to be significantly overexpressed in osteosarcoma (OS) cells. FBXW11, a vital F-box protein of the ubiquitin-proteasome system, mediates the proliferation and survival of cancer cells by targeting multiple substrates for degradation. FBXW11 inhibits OS growth and metastasis by antagonizing the beta-catenin/Wnt signaling pathway. Therefore, we hypothesized that miR-221 targets FBXW11 to mediate Wnt signaling and promote OS proliferation. Methods. In this study, we demonstrated the increased expression of miR-221 and FBXW11 in OS tissues and cell lines by real-time polymerase chain reaction (RT-PCR). Moreover, to elucidate the regulatory mechanism(s) of miR-221 and FBXW11 in progression, cell viability and apoptosis were analyzed by the MTT assay and flow cytometry, respectively. Results. The results showed that the overexpression of miR-221 in OS cells dramatically promoted cell growth and cell cycle progression, and inhibited apoptosis, whereas miR-221 inhibitors conversely inhibited proliferation and promoted apoptosis in OS cells. The data also showed that FBXW11 directly targeted miR-221 and miR-221 regulated OS cell proliferation and apoptosis by binding to FBXW11. We further confirmed that miR-221 targeted FBXW11 to promote proliferation and inhibit apoptosis in OS cell lines by inhibiting Wnt signaling. Interpretation and conclusions. Overall, our study revealed a functional mechanism for miR-221 in OS. Further studies will elucidate its role in the progression of OS and inhibiting miR-221 may represent a useful treatment strategy. (C) 2021 IMSS. Published by Elsevier Inc.
引用
收藏
页码:191 / 199
页数:9
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