Department of Orthopedics, Affiliated Hospital of Chengde Medical University, Chengde, China.
Department of Stomatology, Affiliated Hospital of Chengde Medical University, Chengde, China.
Arch Med Res. 2021 Feb;52(2):191-199. doi: 10.1016/j.arcmed.2020.10.017. Epub 2020 Oct 31.
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 β-catenin/Wnt signaling pathway. Therefore, we hypothesized that miR-221 targets FBXW11 to mediate Wnt signaling and promote OS proliferation.
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.
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.
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.
微小 RNA 在多种癌症的进展中发挥着关键作用，并且已观察到微小 RNA-221（miR-221）在骨肉瘤（OS）细胞中显著过表达。FBXW11 是泛素-蛋白酶体系统的重要 F 盒蛋白，通过靶向多种底物进行降解来调节癌细胞的增殖和存活。FBXW11 通过拮抗 β-连环蛋白/Wnt 信号通路抑制 OS 生长和转移。因此，我们假设 miR-221 靶向 FBXW11 以介导 Wnt 信号并促进 OS 增殖。
在本研究中，我们通过实时聚合酶链反应（RT-PCR）证实 miR-221 和 FBXW11 在 OS 组织和细胞系中的表达增加。此外，为了阐明 miR-221 和 FBXW11 在进展中的调节机制，我们分别通过 MTT 测定法和流式细胞术分析了细胞活力和细胞凋亡。
结果表明，OS 细胞中 miR-221 的过表达可显著促进细胞生长和细胞周期进程，并抑制细胞凋亡，而 miR-221 抑制剂则相反地抑制了 OS 细胞的增殖并促进了其凋亡。数据还表明，FBXW11 直接靶向 miR-221，并且 miR-221 通过结合 FBXW11 调节 OS 细胞增殖和凋亡。我们进一步证实，miR-221 通过抑制 Wnt 信号通路靶向 FBXW11 来促进 OS 细胞系的增殖和抑制凋亡。
总体而言，我们的研究揭示了 miR-221 在 OS 中的功能机制。进一步的研究将阐明其在 OS 进展中的作用，抑制 miR-221 可能代表一种有用的治疗策略。
