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Circ_CLIP2 promotes glioma progression through targeting the miR-195-5p/HMGB3 axis

  • Laboratory Investigation
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Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Background

Circular RNA (circRNA) has been demonstrated to play key roles in regulating glioma progression. Understanding the regulatory mechanism of circRNA in glioma is vital to reveal the pathogenesis of glioma and develop novel therapeutic strategies. Therefore, our study focuses on the role and underlying mechanism of Circ_CLIP2 in glioma.

Methods

The expression of Circ_CLIP2, miR-195-5p and HMGB3 in glioma cells and tissues were analyzed using qRT-PCR. Cell proliferation was determined with colony formation and MTT assays. Cell cycle and apoptosis were examined by flow cytometry. Western blot was conducted for analyzing HMGB3, PCNA, Bax, Bcl-2, cleaved-caspase 3, Wnt-1 and β-catenin. Dual-luciferase reporter assay was measured to investigate the interaction among Circ_CLIP2, miR-195-5p and HMGB3.

Results

The expression of Circ_CLIP2 and HMGB3 were increased while miR-195-5p was down-regulated in glioma cells and patients. Silencing of Circ_CLIP2 inhibited cell proliferation, enhanced cell apoptosis and inhibited the Wnt/β-catenin signaling pathway. Circ_CLIP2 suppressed miR-195-5p expression by directly sponging miR-195-5p. MiR-195-5p inhibited HMGB3 expression via directly targeting HMGB3. Knockdown of miR-195-5p facilitated cell proliferation, inhibited cell apoptosis and activated Wnt/β-catenin signaling, which were reversed by silencing of HMGB3.

Conclusion

Knockdown of Circ_CLIP2 suppresses glioma progression by targeting miR-195-5p/HMGB3 thus inhibiting Wnt/β-catenin signaling. This study may provide potential therapeutic targets against glioma.

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Data availability

All data generated or analysed during this study are included in this published article.

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Funding

This work was supported by Jiangxi provincial department of education natural science foundation youth project (Grant No. GJJ180153), Science and technology plan of Jiangxi provincial health commission (Grant No. 20201063) and National Natural Science Foundation of China (Grant No. 81760445).

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Authors and Affiliations

  1. Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, Jiangxi Province, People’s Republic of China

    Bing Xiao, Shi-gang Lv, Miao-jing Wu, Xiao-li Shen, Wei Tu, Min-hua Ye & Xin-gen Zhu

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  1. Bing Xiao
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  2. Shi-gang Lv
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  3. Miao-jing Wu
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  4. Xiao-li Shen
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  5. Wei Tu
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  6. Min-hua Ye
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  7. Xin-gen Zhu
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Contributions

BX: conceptualization, writing—original draft preparation, validation, visualization, investigation, methodology; SL: methodology; MW: software; XS: data curation; WT: visualization; MY: conceptualization, writing- original draft preparation, supervision, writing—reviewing and editing; XZ: conceptualization, writing—original draft preparation, supervision, writing—reviewing and editing.

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Correspondence to Min-hua Ye or Xin-gen Zhu.

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Our study was approved by the Ethics Committee of Second Affiliated Hospital of Nanchang University.

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Xiao, B., Lv, Sg., Wu, Mj. et al. Circ_CLIP2 promotes glioma progression through targeting the miR-195-5p/HMGB3 axis. J Neurooncol 154, 131–144 (2021). https://doi.org/10.1007/s11060-021-03814-7

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