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CircZNF236 facilitates malignant progression in oral squamous cell carcinoma by sequestering miR-145-5p

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Abstract

Background

A number of non-coding circular RNAs (circRNAs) have recently been implicated in the modulation of gene expression in cancer models. We therefore sought to explore if circZNF236 has a role in oral squamous cell carcinoma (OSCC).

Methods

We first examined circZNF236 expression in 32 pairs of OSCC and noncancerous tissues. We then investigated a functional role for circZNF236 using knockdown and overexpression approaches in OSCC cancer cell lines. Cell counting kit-8, wound healing, Transwell, and flow cytometry were employed to assess circZNF236 function in vitro. The association between circZNF236 and miR-145-5p, or that between miR-145-5p and malignant brain tumor domain containing 1 (MBTD1) was predicted by bioinformatics and demonstrated by dual-luciferase reporter assays, RNA pull-down assays as well as RNA immunoprecipitation (RIP) assays. A mouse OSCC xenograft model was employed to demonstrate the impacts of circZNF236 inhibition on tumor development in vivo.

Results

OSCC tissues and cells had higher levels of circZNF236 expression compared with normal controls. Furthermore, high circZNF236 levels in patients with OSCC correlated with a poor prognosis. CircZNF236 silencing decreased the malignant properties of OSCC cells and suppressed OSCC tumor formation in the mouse model. We then noticed that miR-145-5p can be regulated by circZNF236, and that circZNF2361 promoted OSCC development by absorbing miR-145-5p and consequently upregulating MBTD1 expression.

Conclusion

CircZNF236 modulates OSCC via the miR-145-5p/MBTD1 axis. These results support the potential of circZNF236 as a treatment target for OSCC.

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Data availability

Additional data can be obtained from the corresponding author.

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Acknowledgements

Language assistance in this manuscript was provided by TopEdit (https://www.topeditsci.com).

Funding

Our study was financed by the China Postdoctoral Science Foundation (2020M670865) and Natural Science Foundation of Jilin Province (YDZJ202201ZYTS251).

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Authors and Affiliations

  1. Department of General Dentistry, Hospital of Stomatology, Jilin University, Changchun, China

    Qing Lu

  2. School of Dentistry, Beihua University, Jilin, China

    Hongze Che

  3. Department of Science and Education, Hospital of Stomatology, Jilin University, Changchun, China

    Yanhai Che

  4. Department of Orthodontic, Hospital of Stomatology, Jilin University, 1500 Qing Hua Road, Changchun, 130021, Jilin, China

    Min Hu

  5. Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Changchun, China

    Min Hu

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  1. Qing Lu
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  4. Min Hu
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Contributions

QL and MH conceived the experiments. YC and HC performed the experiments. QL wrote the article. All authors made contributions to the study and approved publication of this work.

Corresponding author

Correspondence to Min Hu.

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Conflict of interest

We declare no conflicting interests.

Ethical approval

Our research was permitted and supervised by the Ethics Committee of Stomatological Hospital of Jilin University. The OSCC patients were treated in line with the Deceleration of Helsinki and granted signed informed consent. The experiments with mice were permitted and supervised by the Ethics Committee of the First Hospital of Jilin University.

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Informed consent was obtained from all individual participants included in the study.

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Lu, Q., Che, H., Che, Y. et al. CircZNF236 facilitates malignant progression in oral squamous cell carcinoma by sequestering miR-145-5p. Clin Transl Oncol 25, 1690–1701 (2023). https://doi.org/10.1007/s12094-022-03064-7

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  • DOI: https://doi.org/10.1007/s12094-022-03064-7

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