American Association for Cancer Research
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Supplementary Figure 3 from Downregulation of miR-452 Promotes Stem-Like Traits and Tumorigenicity of Gliomas

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posted on 2023-03-31, 17:53 authored by Liping Liu, Kun Chen, Jueheng Wu, Ling Shi, Bo Hu, Shiyuan Cheng, Mengfeng Li, Libing Song

miR-452 directly targets Bmi-1, LEF1 and TCF4.



Purpose: miR-452 is reported to be required for neural crest stem cell differentiation during neural crest development. However, the biologic role of miR-452 in gliomas remains unclear. The aim of the present study was to evaluate the effect of miR-452 on the stem-like properties and tumorigenesis of glioma cells.Experimental Design: The expression of miR-452 was examined in glioma cells and glioma tissues using real-time PCR. The effects of miR-452 on stem-like traits and tumorigenesis were investigated in vitro and in vivo using patient-derived glioma cells and glioma cell lines. Western blotting and luciferase reporter assays were conducted to examine the negative regulation of Bmi-1, LEF1, and TCF4 by miR-452. The methylation of the miR-452 promoter region was examined by bisulfite genomic sequencing PCR.Results: miR-452 was markedly downregulated in glioma cells and clinical glioma tissues. miR-452 levels were inversely correlated with World Health Organization (WHO) grades and patient survival. miR-452 directly targeted and suppressed multiple stemness regulators, including Bmi-1, LEF1, and TCF4, resulting in reduced stem-like traits and tumorigenesis of glioma cells in vitro and in vivo. Furthermore, we showed that downregulation of miR-452 in gliomas was caused by hypermethylation of its promoter region.Conclusions: Downregulation of miR-452 plays an important role in promoting the stem-like traits and tumorigenesis of gliomas and may represent a novel prognostic biomarker and therapeutic target for the disease. Clin Cancer Res; 19(13); 3429–38. ©2013 AACR.