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miR-429 inhibits glioma invasion through BMK1 suppression

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Abstract

The purpose of this research was to examine the relationship between big mitogen-activated protein kinase 1 (BMK1) and miRNA miR-429 and to determine the effect of miR-429 on glioma invasiveness. Immunohistochemistry was used to evaluate BMK1 expression in glioma tissues. Real-time PCR was used to measure the expression of miR-429 and other RNAs. Western blot was used to detect the expression of BMK1 and other related proteins. Wound healing, Matrigel invasion, and chemotaxis assays were performed to detect the invasion and migration of glioma cell lines. The actual binding site of miR-429 to the 3′ untranslated region of BMK1 was confirmed by luciferase assay and RNA immunoprecipitation. BMK1 expression was associated with the World Health Organization grading of glioma and inversely correlated with patient survival. Suppression of BMK1 inhibited the migration and invasion of glioma cells by interfering with mesenchymal transition. Additionally, hepatocyte growth factor-induced GSK3β phosphorylation was suppressed through BMK1 knockdown. Interestingly, our findings validated a novel role for miR-429 in suppressing the migration and invasion of glioma by directly inhibiting BMK1 expression. We also found that miR-429 expression in glioma cells and tissues was lower than that in normal cells and adjacent non-neoplastic tissues, and miR-429 overexpression inhibited invasive activity of glioma cells both in vitro and in vivo. Furthermore, our data validated that miR-429 downregulation was due to the hypermethylation of its promoter region. Our results indicated that BMK1 modulation by miR-429 has an important function in glioma invasion both in vitro and in vivo.

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Acknowledgments

This work was supported by National Natural Scientific Foundation of China (81072068,81472365), Scientific Foundation of Shandong Province(ZR2014HM003, 2014ZRB14097),The Young and Middle-Aged Scientists Research Awards Fundation of Shandong Province (2010BSB14050), Foundation of Shandong Educational Committee (J14LK13).

Author contributions

Conception and design: Baogang Zhang; Financial support and designed research: Baogang Zhang and Weiyi Chen; Performed research and analyzed data: Weiyi Chen, Baogang Zhang, Wenjun Guo, Linlin Gao, Lihong Shi, Hongli Li, Shijun Lu, Yuqing Liu and Xiaolong Li. All authors have read and approved the final manuscript.

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    Authors and Affiliations

    1. Department of Pathology, Weifang Medical University, Weifang, 261053, People’s Republic of China

      Weiyi Chen, Baogang Zhang, Wenjun Guo, Shijun Lu, Yuqing Liu & Xiaolong Li

    2. Department of Internal Medicine, NO.3, Laixi Municipal Hospital, Laixi, 266600, People’s Republic of China

      Linlin Gao

    3. Department of Pharmacology, Weifang Medical University, Weifang, 261053, People’s Republic of China

      Lihong Shi

    4. Department of Medicine Research Center, Weifang Medical University, Weifang, 261053, People’s Republic of China

      Hongli Li

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    1. Weiyi Chen
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    Weiyi Chen and Baogang Zhang have contributed equally to this work.

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    Chen, W., Zhang, B., Guo, W. et al. miR-429 inhibits glioma invasion through BMK1 suppression. J Neurooncol 125, 43–54 (2015). https://doi.org/10.1007/s11060-015-1887-x

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