Abstract
Transforming growth factor-β (TGF-β) is considered to be one of the main factors responsible for glioblastoma tumorigenesis. MicroRNAs have recently been shown to regulate cell proliferation, differentiation, and apoptosis. However, the involvement of miRNA-146a in TGF-β1-induced glioblastoma development remains largely unknown. Here, miRNA-164a transfection was used to overexpress miRNA-164a in U87, and then real-time quantitative PCR and Western blot were applied to detect the gene transcription and protein expression. In addition, MTT and wound healing assay were also used to observe cell proliferation and migration. Our data revealed that miRNA-146a was downregulated by TGF-β1 treatment, but upregulated by miRNA-164a transfection. MiRNA-146a overexpression significantly reduced SMAD4 protein expression instead of p-SMAD2. Besides, miRNA-146a overexpression also decreased the messenger RNA (mRNA) and protein expression of epidermal growth factor receptor (EGFR) and MMP9 as well as the p-ERK1/2 level. Furthermore, the upregulation of miRNA-146a suppressed TGF-β1-mediated U87 proliferation and migration. These results demonstrate that miRNA-146a acts as a novel regulator to modulate the activity and transduction of TGF-β signaling pathways in glioblastoma, and the downregulation of miRNA-146a is required for overexpression of EGFR and MMP9, which can be considered an efficiently therapeutic target and a better understanding of glioblastoma pathogenesis.
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Acknowledgments
This study was supported by the Institute Project of Shandong Provincial Academy of Medical Sciences (2013015). We greatly thank Huihui Kang in Sandy lab for valuable suggestions and writing.
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The authors state that there are no conflicts of interest to disclose.
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Shunzeng Lv and Bowen Sun contributed equally to this work.
This article has been retracted at the request of the Editor-in-Chief and the Publisher per the Committee on Publication Ethics guidelines. The article shows evidence of irregularities in authorship during the submission process and there is strong reason to believe that the peer review process was compromised.
An erratum to this article is available at http://dx.doi.org/10.1007/s12035-017-0452-3.
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Lv, S., Sun, B., Dai, C. et al. RETRACTED ARTICLE: The Downregulation of MicroRNA-146a Modulates TGF-β Signaling Pathways Activity in Glioblastoma. Mol Neurobiol 52, 1257–1262 (2015). https://doi.org/10.1007/s12035-014-8938-8
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DOI: https://doi.org/10.1007/s12035-014-8938-8