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Circ_0058063 Contributed to Oral Squamous Cell Carcinoma Development by Sponging miR-145 and Regulating PI3K/AKT Pathway

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Abstract

Background

Circular RNAs (circRNAs) are key regulators of oral squamous cell carcinoma (OSCC) progression. In this study, we aimed to clarify the regulatory roles of circ_0058063 and its effect on tumorigenesis in OSCC.

Methods

Quantitative real-time polymerase chain reaction was conducted to determine the expression levels of microRNA (miR)-145-5p and circ_0058063 in OSCC. Cell viability, adhesion, migration, and epithelial–mesenchymal transition (EMT) of OSCC cells were assessed using cell counting kit-8, cell adhesion, and transwell assays. Western blotting was performed to determine the phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) phosphorylation levels. Xenograft tumor models were constructed to evaluate the tumorigenicity of OSCC cells in vivo. In addition, the interaction between circ_0058063 and miR-145-5p was validated via luciferase reporter and RNA immunoprecipitation assays.

Results

Expression levels of circ_0058063 were elevated, whereas those of miR-145-5p were decreased in OSCC. Upregulation of circ_0058063 levels enhanced the viability, adhesion, migration, and EMT of OSCC cells in vitro and promoted tumorigenicity in vivo. Moreover, circ_0058063 promoted OSCC growth by upregulating the PI3K and AKT phosphorylation levels. miR-145-5p overexpression considerably inhibited the PI3K/AKT pathway and decreased OSCC cell viability, adhesion, migration, and EMT. Mechanistically, circ_0058063 sponged miR-145-5p and activated the PI3K/AKT pathway in OSCC cells.

Conclusion

Our results revealed that circ_0058063 functions as an oncogene via regulation of the PI3K/AKT pathway by targeting miR-145-5p in OSCC, suggesting its potential for OSCC diagnosis and treatment.

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Data Availability

The datasets used and/or analyzed throughout this present investigation are available from the corresponding author upon proper request.

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Acknowledgements

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Funding

This work was supported by the Wuhan Municipal Health Fund (Project Number: S202204200035), [Grant Number: WZ22B05].

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Authors and Affiliations

  1. Department of Stomatology, Wuhan Fourth Hospital, No. 473, Hanzheng Street, Qiaokou District, Wuhan, 430030, Hubei, China

    Jie Zhou & Song Jin

Authors
  1. Jie Zhou
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  2. Song Jin
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Contributions

JZ conducted the experiments and data analysis. SJ designed this study and formed the methodology. JZ did investigation. SJ authored the paper. This manuscript was reviewed and revised by JZ and SJ. This work has been reviewed and approved by all authors.

Corresponding author

Correspondence to Song Jin.

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The authors stated that they did not have any conflicts of interest.

Ethical Approval

Wuhan Fourth Hospital's Ethics Committee approved this study (Wuhan, China). The World Medical Association's Helsinki Declaration was observed during the conduct of this study. All enrolled patients signed informed consent papers.

The animal experiments had been approved by the Animal Protection and Use Committee of the Wuhan Fourth Hospital. The ARRIVE standards have been strictly followed in all of the animal investigations.

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All patients signed written informed consent.

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Zhou, J., Jin, S. Circ_0058063 Contributed to Oral Squamous Cell Carcinoma Development by Sponging miR-145 and Regulating PI3K/AKT Pathway. Mol Biotechnol 65, 2049–2060 (2023). https://doi.org/10.1007/s12033-023-00715-0

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  • DOI: https://doi.org/10.1007/s12033-023-00715-0

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