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Silent FOSL1 Enhances the Radiosensitivity of Glioma Stem Cells by Down-Regulating miR-27a-5p

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Abstract

Since few reports have mentioned the role of FOSL1 in the radiotherapy sensitivity of glioma, this study would dig deep into this aspect. Cancer stem cells (CSCs) isolated by magnetic bead assay were identified by microscopy, qRT-PCR and western blot. The number of apoptotic cells was counted 72 h after X-ray irradiation to evaluate the sensitivity of cancer cells to radiotherapy. The effects of radiotherapy, FOSL1 and miR-27a-5p on basic cell functions were detected by functional experiments. The expressions of FOSL1, apoptosis-related genes and miR-27a-5p were detected by qRT-PCR and western blot as needed. The differential expression of FOSL1 and the effect of miR-27a-5p on survival rate were analyzed using GEPIA and UALCAN, respectively. FOSL1 was found highly expressed in glioma cells and patients. The appearance of spherical cells and high expressions of CSC-related markers indicated the successful isolation of CSC-like cells. The increment of X-ray dose enhanced the sensitivity of cancer cells to radiotherapy. Radiotherapy down-regulated cell viability and the expressions of FOSL1 and Bcl-2, but up-regulated cell apoptosis and the expressions of cleaved caspase-3 and Bax, which could be partially reversed by overexpressed FOSL1 or further enhanced by shFOSL1. MiR-27a-5p was highly expressed in in patients with glioma, which was associated with poor prognosis, while shFOSL1-inhibited miR-27a-5p expression enhanced the sensitivity of glioma stem cells to radiotherapy. In vivo experiments further verified the results obtained from in vitro experiments. Silent FOSL1 strengthened the radiosensitivity of glioma by down-regulating miR-27a-5p.

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Data Availability

The analyzed data sets generated during the study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Radiation Oncology, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

    Rong Li

  2. Department of Neurosurgery, Kunming Children’s Hospital, No. 288, Qianxing Road, Kunming, 650030, China

    Wuqiang Che, Naizheng Liang, Shu Deng, Zhijie Song & Lei Yang

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  1. Rong Li
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  6. Lei Yang
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Contributions

RL: Substantial contributions to conception and design. WC, NL, SD, ZS, LY: Data acquisition, data analysis and interpretation. RL: Drafting the article or critically revising it for important intellectual content. RL, WC, NL, SD, ZS, LY: Final approval of the version to be published. RL, WC, NL, SD, ZS, LY: Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of the work are appropriately investigated and resolved.

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Correspondence to Lei Yang.

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Animal experiments involved in this study were approved by the Animal Experiment Ethics Committee of the First Affiliated Hospital, Guangzhou Medical University (FG201907010NWK).

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Li, R., Che, W., Liang, N. et al. Silent FOSL1 Enhances the Radiosensitivity of Glioma Stem Cells by Down-Regulating miR-27a-5p. Neurochem Res 46, 3222–3246 (2021). https://doi.org/10.1007/s11064-021-03427-6

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