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Circular RNA circ_0000741/miR-379-5p/TRIM14 signaling axis promotes HDAC inhibitor (SAHA) tolerance in glioblastoma

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Abstract

Background

Histone deacetylase (HDAC) inhibitor-based therapeutic drug tolerance is a major obstacle to glioblastoma (GBM) treatment. Meanwhile, non-coding RNAs have been reported to be involved in the regulation of HDAC inhibitor (SAHA) tolerance in some human tumors. However, the relationship between circular RNAs (circRNAs) and SAHA tolerance is still unknown. Herein, we explored the role and mechanism of circ_0000741 on SAHA tolerance in GBM.

Methods

Circ_0000741, microRNA-379-5p (miR-379-5p), and tripartite motif-containing 14 (TRIM14) level were detected by real-time quantitative polymerase chain reaction (RT-qPCR). (4-5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), 5-ethynyl-2’-deoxyuridine (EdU), Colony formation, flow cytometry, and transwell assays were used to detect SAHA tolerance, proliferation, apoptosis, and invasion in SAHA-tolerant GBM cells. Western blot analysis of protein levels of E-cadherin, N-cadherin, and TRIM14. After Starbase2.0 analysis, the binding between miR-379-5p and circ_0000741 or TRIM14 was proved using a dual-luciferase reporter. The role of circ_0000741 on drug tolerance was assessed using a xenograft tumor model in vivo.

Results

Circ_0000741 and TRIM14 were upregulated, and miR-379-5p was reduced in SAHA-tolerant GBM cells. Furthermore, circ_0000741 absence reduced SAHA tolerance, suppressed proliferation, invasion, and induced apoptosis in SAHA-tolerant GBM cells. Mechanistically, circ_0000741 might affect TRIM14 content via sponging miR-379-5p. Besides, circ_0000741 silencing enhanced the drug sensitivity of GBM in vivo.

Conclusion

Circ_0000741 might accelerate SAHA tolerance by regulating the miR-379-5p/TRIM14 axis, which provided a promising therapeutic target for GBM treatment.

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Data availability

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

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Acknowledgements

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Funding

This study was supported by Basic Research project of Knowledge Innovation Plan of Wuhan Science and Technology Bureau (Grant Agreement number: 2022020801010549) and The Seventh Batch of Wuhan Young and Middle-aged Medical Backbone Talents Project.

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Authors and Affiliations

  1. Department of Neurosurgery, Wuhan Third Hospital, Tongren Hospital of Wuhan University, 430060, Wuhan, China

    Liang Meng, Yuefei Wang, Qin Tu & Yuan Zhu

  2. Department of 120 treatment center, Wuhan Third Hospital, Tongren Hospital of Wuhan University, 430060, Wuhan, China

    Xiaoqin Dai

  3. Department of Medical Laboratory, Wuhan Third Hospital, Tongren Hospital of Wuhan University, No.241, Pengliuyang Road, Wuchang District, 430060, Wuhan, China

    Ji Yang

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  1. Liang Meng
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Contributions

J.Y. designed the research study. L.M. and Y.W. performed the research. Q.T. collected and analyzed the data. Y.Z. contributed essential reagents or tools. X.D. operated the software and wrote the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Ji Yang.

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Approval to perform this animal experiment was acquired from the Wuhan Third Hospital.

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Meng, L., Wang, Y., Tu, Q. et al. Circular RNA circ_0000741/miR-379-5p/TRIM14 signaling axis promotes HDAC inhibitor (SAHA) tolerance in glioblastoma. Metab Brain Dis 38, 1351–1364 (2023). https://doi.org/10.1007/s11011-023-01184-9

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