Zhao Ruibo, He Hongbo, Zhu Yong, Wan Jun, Li Yusheng, Gao Shuguang, Zhang Can
Pharmazie. 2017 Oct 1;72(10):593-598. doi: 10.1692/ph.2017.7574.
Hyperproliferation of cells is a major problem is osteosarcoma (OS). So, further elucidation of the molecular mechanisms underlying hyperproliferation of OS is needed. Western blots results showed that 14-3-3ζ protein was upregulated in OS cell lines; 14-3-3ζ knockdown significantly suppressed OS cell proliferation, as well as the protein levels of p-STAT3, c-Myc and Cyclin D1. MicroRNA-204 (miR-204) has been regarded as an essential regulator in cancer carcinogenesis, including OS. Here, we revealed that miR-204 directly targets the 3'UTR of 14-3-3ζ to inhibit its expression, thus to suppress 14-3-3ζ -induced OS cell hyperproliferation. Further, we demonstrated that the STAT3 pathway was involved in miR-204/14-3-3ζ regulation of OS cell proliferation. Our findings provide information about the underlying mechanisms of miR-204/14-3-3ζ in OS cell proliferation through the STAT3 pathway, and suggest miR-204 and 14-3-3ζ as potential therapeutic targets in OS.
细胞过度增殖是骨肉瘤（OS）的一个主要问题。因此，需要进一步阐明骨肉瘤细胞过度增殖的分子机制。蛋白质免疫印迹结果显示，14-3-3ζ蛋白在骨肉瘤细胞系中表达上调；敲低14-3-3ζ可显著抑制骨肉瘤细胞增殖，以及p-STAT3、c-Myc和细胞周期蛋白D1的蛋白水平。微小RNA-204（miR-204）被认为是包括骨肉瘤在内的癌症发生过程中的一种重要调节因子。在此，我们发现miR-204直接靶向14-3-3ζ的3'非翻译区以抑制其表达，从而抑制14-3-3ζ诱导的骨肉瘤细胞过度增殖。此外，我们证明信号转导和转录激活因子3（STAT3）通路参与了miR-204/14-3-3ζ对骨肉瘤细胞增殖的调控。我们的研究结果提供了关于miR-204/14-3-3ζ通过STAT3通路调控骨肉瘤细胞增殖的潜在机制的信息，并提示miR-204和14-3-3ζ作为骨肉瘤潜在的治疗靶点。
