miR‑143 acts as a novel Big mitogen‑activated protein kinase 1 suppressor and may inhibit invasion of glioma

miR-143 可作为新型大丝裂原活化蛋白激酶 1 抑制剂,并可能抑制神经胶质瘤的侵袭

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作者:Wei-Yi Chen, Zhi-Qiang Lang, Chao Ren, Ping Yang, Baogang Zhang

Abstract

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.

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