Chlorotoxin fusion protein regulates miR-374a and TNFAIP8 expression and inhibits glioma cell proliferation and promotes
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ORIGINAL ARTICLE
Chlorotoxin fusion protein regulates miR-374a and TNFAIP8 expression and inhibits glioma cell proliferation and promotes apoptosis Zhen Yuan . Baihui Zhang . Jingling Zhuang . Xu Yang . Jiawen Yu . Qiang Xu . Nasir Azam . Khalil ur Rahman . Bin Feng
Received: 9 January 2020 / Accepted: 8 July 2020 Ó Springer Nature B.V. 2020
Abstract Glioblastoma multiforme is the most common primary central nervous system malignancy, accounting for half of all intracranial primary tumors. In this study we constructed a multifunctional chlorotoxin fusion protein E-CHP that combines enhanced green fluorescent protein (E), glioma-targeting peptide chlorotoxin (C), destabilizing lipid membrane peptide riHA2 (H), and C-terminal and mouse double minute domains of p53 (P). E-CHP was expressed in Escherichia coli and purified by His affinity chromatography. Fluorescence microscopy observation showed that E-CHP could effectively target glioma cells; real-time quantitative PCR revealed that E-CHP increased miR-374a expression; and the dual
luciferase reporter assay showed that tumor necrosis factor alpha-induced protein (TNFAIP)8 is a direct target of miR-374a. E-CHP and miR-374a inhibited the proliferation and migration of glioma cells, and Western blot analysis indicated that they suppressed TNFAIP8 expression in glioma cells and promoted the expression of caspase-3 and -8. Finally, E-CHP and miR-374a stimulated the apoptosis of glioma cells, as determined by flow cytometry analysis. These results suggest that miR-374a is a new candidate target for glioma therapy, whereas E-CHP fusion protein has the potential to be developed as a multifunctional carrier for targeted drug delivery and therapy. Keywords Glioma miR-374a TNFAIP8 Chlorotoxin fusion protein Targeted therapy
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10616-020-00411-w) contains supplementary material, which is available to authorized users. Z. Yuan B. Zhang J. Zhuang X. Yang N. Azam K. ur Rahman B. Feng (&) Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China e-mail: [email protected] J. Yu Department of Hematology, The First Affiliated Hospital of Dalian Medical University, Dalian, China Q. Xu Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian, China
Introduction Glioblastoma multiforme, also known as glioma, is the most common and highly malignant primary central nervous system tumor, accounting for about half of all primary intracranial tumors (Nabors et al. 2017). Owing to its invasive growth, high rate of recurrence, and resistance to radiation and drugs, surgical resection, radiotherapy, and chemotherapy are not effective in the treatment of glioma. The average survival time of glioma patients is just 12 to 14 months, and the
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Cytotechnology
3-year survival rate is 3–5% (Alexander and Cloughesy 2017; Nabors et al.
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