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MicroRNA-640 Inhibition Enhances the Chemosensitivity of Human Glioblastoma Cells to Temozolomide by Targeting Bcl2 Modifying Factor

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Abstract

Glioblastoma (GBM) is the most malignant and challenging type of astrocytoma and also notoriously acknowledged as the most common primary brain tumor globally. Currently, chemotherapy is the most master therapy for tumor and is essential in clinical treatment for GBM. Nevertheless, the characterization of chemotherapy resistance seriously hinders clinical chemotherapy treatment. Accordingly, there are imperious demands for the exploitation of novel chemosensitizer to promote the efficacy of chemotherapy. Our current study was conducted to probe into the potential impacts of microRNA (miR)-640 on the chemosensitivity in GBM and the associated underlying mechanism. Initially, TargetScan software was utilized to predict the targeted genes of miR-640, and the target relationship between miR-640 and Bcl-2-modifying factor (BMF) was validated by double luciferase report assay. Additionally, to explore the role of miR-640/BMF in U251 cells, miR-640 inhibitor/BMF-siRNA was used. U251 cells were processed with 100 μM temozolomide (TMZ) and detected with CCK-8 kit. Eventually, RT-qPCR and Western blotting were used for evaluating Bcl-2, Bax mRNA, and protein expression level. Flow cytometry analysis was performed to measure cellular apoptosis. Initially, the results indicated that BMF was the target gene of miR-640. MiR-640 negatively regulated BMF expression in GBM cells. Besides, the findings revealed that miR-640 inhibition significantly inhibited U251 cell proliferation, promoted cell apoptosis, and increased the sensitivity of GBM cells to TMZ by targeting BMF. Moreover, BMF overexpression significantly suppressed U251 cell proliferation, induced cell apoptosis, and increased the sensitivity of GBM cells to TMZ. Inhibition of miR-640 expression enhances chemosensitivity of human GBM cells to TMZ by targeting BMF.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by the Scientific Research Project of Wuhan Municipal Health Commission (Grant No. WX21C05).

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  1. Shu Jiang and Chao Luo have contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics, Wuhan Fourth Hospital, No. 76 Jiefang Avenue, Qiaokou District, Wuhan, 430034, China

    Shu Jiang, Chao Luo, Yongli Chen, Jing Chen, Shuang Tao, Quan Zou, Chunzhi He & Shanwu Dong

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  1. Shu Jiang
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  2. Chao Luo
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  3. Yongli Chen
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  4. Jing Chen
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  5. Shuang Tao
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  6. Quan Zou
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  7. Chunzhi He
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  8. Shanwu Dong
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Contributions

SJ and CL contributed to the study design, data collection, statistical analysis, data interpretation, and manuscript preparation. YC, JC, ST, and QZ contributed to data collection and statistical analysis. CH and SD contributed to data collection, statistical analysis, and manuscript preparation. All authors read and approved the final manuscript.

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Correspondence to Chunzhi He or Shanwu Dong.

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Jiang, S., Luo, C., Chen, Y. et al. MicroRNA-640 Inhibition Enhances the Chemosensitivity of Human Glioblastoma Cells to Temozolomide by Targeting Bcl2 Modifying Factor. Biochem Genet 61, 538–550 (2023). https://doi.org/10.1007/s10528-022-10264-x

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  • DOI: https://doi.org/10.1007/s10528-022-10264-x

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