Department of Pathology, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
Department of Pathology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China.
Oncol Rep. 2019 Sep;42(3):1194-1204. doi: 10.3892/or.2019.7218. Epub 2019 Jul 3.
Upregulation of the Big mitogen‑activated protein kinase (BMK)1 has been reported in glioma and other epithelial tumors. In addition, the decreased expression of BMK1 inhibits tumorigenesis, leading to the broad consensus that it functions as cell‑autonomous epithelial tumor promoter. Using two online miRNA target prediction databases, microRNA (miR)‑143 was predicted as the potential miRNA regulator of BMK1. RNA immunoprecipitation analysis and Luciferase reporter assay showed that miR‑143 binds to the 3' untranslated region of BMK1. Notably, the expression of miR‑143 has a strong association with the World Health Organization grade and survival rates in patients with glioma by statistical analysis. Furthermore, miR‑143 inhibited glioma cells migration and invasion through cytoskeletal rearrangement in vitro and in vivo through matrigel invasion assay, scratch assay, cellular F‑actin measurement, chemotaxis assay and intracranial brain tumor xenografts. Finally, DNA methylation assay showed that the downregulation of miR‑143 was due to hypermethylation of its promoter region. These results reveal that miR‑143 represents a potential therapeutic target in glioma by modulating BMK1.
Big 丝裂原活化蛋白激酶 1（BMK1）的上调已在神经胶质瘤和其他上皮肿瘤中报道。此外，BMK1 的表达减少抑制了肿瘤发生，导致广泛共识认为它作为自主上皮肿瘤促进剂发挥作用。使用两个在线 microRNA（miRNA）靶标预测数据库，预测 miRNA-143 是 BMK1 的潜在 miRNA 调节剂。RNA 免疫沉淀分析和荧光素酶报告基因分析显示，miR-143 结合到 BMK1 的 3'非翻译区。值得注意的是，通过统计分析，miR-143 的表达与神经胶质瘤患者的世界卫生组织分级和生存率具有很强的相关性。此外，miR-143 通过体外和体内基质胶侵袭试验、划痕试验、细胞 F-肌动蛋白测量、趋化性试验和颅内脑肿瘤异种移植，通过细胞骨架重排抑制神经胶质瘤细胞迁移和侵袭。最后，DNA 甲基化试验表明，miR-143 的下调是由于其启动子区域的高甲基化。这些结果表明，miR-143 通过调节 BMK1 成为神经胶质瘤的潜在治疗靶点。
