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Hsa_circ_0000078 Regulates miR-205-5p/EREG Pathway to Inhibit Cervical Cancer Progression

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Abstract

It is well established that circular RNAs (circRNAs) play a role in tumor initiation and tumorigenesis. The goal of this study was to reveal the detailed functions and regulatory mechanisms of circ_0000078 in cervical cancer (CC). Circ_0000078, miR-205-5p, and epiregulin (EREG) mRNA expression levels were examined using RT-qPCR. Western blotting was performed to quantify EREG protein. Cell proliferation, apoptosis, migration, and invasion were examined by performing CCK-8, caspase 3 activity, wound healing, and transwell assays, respectively. The effect of circ_0000078 on tumor growth in vivo was confirmed in a xenograft model. The putative relationship between miR-205-5p and circ_0000078 or EREG, as predicted by bioinformatics analysis, was evaluated by dual-luciferase and RNA immunoprecipitation assays. Aberrant downregulation of circ_0000078 and EREG as well as upregulation of miR-205-5p were observed in cervical tumor samples and cancer cells. Ectopic expression of circ _0000078 not only restrained cancer cell growth, survival, migration, and invasiveness, but also decelerated tumor formation and development in a mouse model. miR-205-5p, acts as a target of circ_0000078 and directly binds to EREG to repress its expression. Overexpression of miR-205-5p reversed the inhibitory effects of circ_0000078 upregulation on cancer cell behavior and also partially abolished the anti-cancer effects of EREG upregulation in vitro. Circ_0000078 inhibits the growth of cancer by interfering with the miR-205-5p/EREG network, acting as a tumor suppressor in CC. These results provide a better understanding of the pathogenesis of this disease.

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Data Availability

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

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Acknowledgements

None.

Funding

This work was supported by 2021 Wuhan Municipal Health Commission scientific research projects: Western medicine and public health "RGD-USPIO targeted nano-contrast agent 4.7T MRI in vivo scanning molecular imaging in precise definition of cervical cancer radiotherapy target", Grant Number: WX21C28.

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Author notes

  1. Can Liu and Yuan Li have contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, Wuhan Fourth Hospital, Wuhan, 430033, Hubei, China

    Can Liu

  2. Department of Obstetrics and Gynecology, Wuhan Fourth Hospital, No. 473, Hanzheng Street, Qiaokou District, Wuhan, 430033, Hubei, China

    Yuan Li

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Contributions

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

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Correspondence to Yuan Li.

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The authors affirm that they do not have any competing interests.

Ethical Approval

The present study was approved by the Ethics Committee of our hospital. The Declaration of Helsinki's ethical guidelines are strictly followed when processing clinical tissue samples. Each patient completed an informed consent form in writing. This animal experiment was conducted in accordance with the ARRIVE guidelines and was authorized by the Ethics Committee of our hospital.

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Liu, C., Li, Y. Hsa_circ_0000078 Regulates miR-205-5p/EREG Pathway to Inhibit Cervical Cancer Progression. Mol Biotechnol 65, 1453–1464 (2023). https://doi.org/10.1007/s12033-023-00658-6

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  • DOI: https://doi.org/10.1007/s12033-023-00658-6

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