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Circular RNA Circ-ITCH Inhibits the Malignant Behaviors of Cervical Cancer by microRNA-93-5p/FOXK2 Axis

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Abstract

Growing evidence has been demonstrated that circular RNA circ-ITCH plays an important role in the development of several cancers. However, the role of circ-ITCH in cervical cancer has not been evaluated. The aim of the present study was to investigate the biological function of circ-ITCH in cervical cancer both in vitro and in vivo. Our results showed that circ-ITCH was lowly expressed in both human cervical cancer tissues and cell lines. Overexpression of circ-ITCH in HeLa cells significantly suppressed cell proliferation, migration, and invasion. A xenograft tumor model was established to evaluate the role of circ-ITCH in vivo. The results showed that overexpression of circ-ITCH significantly inhibited tumorigenesis of cervical cancer. Mechanism investigations proved that circ-ITCH executed its tumor suppressive activity through sponging microRNA-93-5p (miR-93-5p) and regulating the expression of forkhead box K2 (FOXK2). These findings suggest that circ-ITCH may be a therapeutic target for the management of cervical cancer.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, The Third Hospital of Jinan, Jinan, 250132, Shandong province, China

    Jing Li & Ruibao Guo

  2. Department of Infertility, The Third Hospital of Jinan, Jinan, 250132, Shandong province, China

    Qing Liu

  3. Department of Gynecology and Obstetrics, Shanxian Central Hospital, Shanxian, 274300, Shandong Province, China

    Jingli Sun

  4. Department of Gynecology, The Second Hospital of Shandong University, Jinan, 250033, Shandong Province, China

    Huali Wang

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  1. Jing Li
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  2. Ruibao Guo
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  3. Qing Liu
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  4. Jingli Sun
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  5. Huali Wang
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Correspondence to Huali Wang.

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Informed consents were obtained from all patients before the study. The study was approved by the Ethics Committee of the Third Hospital of Jinan.

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Supplementary Fig. 1

The expression of FOXK2 in HeLa cells. (A) qRT-PCR analysis of FXOK2 expression levels after transfection with si-FOXK2 in miR-93-5p inhibitor transfected HeLa cells. (B) Western blot analysis of FOXK2 protein expression levels after transfection with si-FOXK2 in miR-93-5p inhibitor transfected HeLa cells. *p < 0.05 vs anti-NC group; # p < 0.05 vs miR-93-5p inhibitor group (PNG 246 kb).

High resolution image (TIF 2651 kb).

Supplementary Fig. 2

The expression of miR-93-5p and FOXK2 in isolated tumor tissues. After four weeks later, the mice were sacrificed and tumor tissues were separated. (A) qRT-PCR analysis of miR-93-5p expression levels in the isolated tumor tissues. (B and C) qRT-PCR and Western blot analysis of FOXK2 mRNA and protein expression levels in the isolated tumor tissues. *p < 0.05 (PNG 196 kb).

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Li, J., Guo, R., Liu, Q. et al. Circular RNA Circ-ITCH Inhibits the Malignant Behaviors of Cervical Cancer by microRNA-93-5p/FOXK2 Axis. Reprod. Sci. 27, 860–868 (2020). https://doi.org/10.1007/s43032-020-00140-7

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  • DOI: https://doi.org/10.1007/s43032-020-00140-7

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