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CircWHSC1 expedites cervical cancer progression via miR-532-3p/LTBP2 axis

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Abstract

Dysregulated circRNAs have potential roles in the progression of various cancer types, including cervical cancer (CaCx). The carcinogenic roles of circRNA Wolf–Hirschhorn syndrome candidate gene-1 (circWHSC1) are described in the development of diverse cancers. The objective of this study was to investigate the expression and the underlying role of circWHSC1 in CaCx. The expression of circWHSC1 was detected by real-time PCR. After the suppression of circWHSC1 expression, the changes in the proliferation, migration, invasion, and apoptosis capacities were detected by CCK-8 assay, colony formation assay, Transwell assays, flow cytometry, and the determination of apoptosis-related proteins. The interplay among circWHSC1, miR-532-3p, and latent transforming growth factor-β binding protein 2 (LTBP2) was confirmed by luciferase reporter and biotinylated RNA pull-down assays. A nude mice xenograft tumor model was established to evaluate the anti-tumorigenic role of circWHSC1 silencing in vivo. CircWHSC1 was overexpressed in CaCx tissues and cell lines and its high expression was inversely associated with the survival rate of patients with CaCx. CircWHSC1 silencing was capable of suppressing the proliferation, metastasis, and invasion of tumor cells and inducing apoptosis. Investigation to its molecular mechanism revealed that circWHSC1 functioned as a competitive endogenous RNA (ceRNA), mediating LTBP2 expression by targeting miR-532-3p. The in vivo experiments further confirmed the inhibition of tumor growth and metastasis by circWHSC1 knockdown. The circWHSC1-mediated miR-532-3p/LTBP2 signaling axis might be a novel therapeutic target for CaCx.

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Authors and Affiliations

  1. Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China

    Yan Li, Fandong Meng, Chengguang Sui & Yang Wang

  2. Department of Gynaecology and Obstetrics, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, 110000, Liaoning, China

    Dali Cheng

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  1. Yan Li
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  3. Chengguang Sui
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  4. Yang Wang
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  5. Dali Cheng
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Contributions

YL, FDM, and CGS conceived and designed the experiments, YW analyzed and interpreted the results of the experiments, and DC performed the experiments; all authors have read and approved the manuscript.

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Correspondence to Dali Cheng.

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The experiments were approved by the Ethics Committee of Shengjing Hospital of China Medical University.

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Li, Y., Meng, F., Sui, C. et al. CircWHSC1 expedites cervical cancer progression via miR-532-3p/LTBP2 axis. Mol Cell Biochem 477, 1669–1679 (2022). https://doi.org/10.1007/s11010-022-04395-3

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  • DOI: https://doi.org/10.1007/s11010-022-04395-3

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