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FOXN3 inhibits the progression of ovarian cancer through negatively regulating the expression of RPS15A

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Abstract

Ovarian cancer is the second most common cause of gynecological cancer death and has a high recurrence rate. FOXN3, a transcription inhibitor belonging to FOX family, has anti-tumor effects on several cancers. Bioinformatics analysis revealed that the expression of FOXN3 was downregulated in ovarian cancer specimens. However, the role of FOXN3 in ovarian cancer remains unclear. Herein, we investigated the role of FOXN3 in ovarian cancer using OVCAR3 and A2780 cells. Flow cytometry and CCK-8 analysis showed that overexpression of FOXN3 inhibited the proliferation and cell cycle progression of OVCAR3 cells. Cell invasion and migration abilities were decreased by FOXN3 according to transwell and wound healing assays. The suppression of FOXN3 on angiogenesis in OVCAR3 cells was evidenced by reduced vessel formation and VEGFA protein expression. Taken together, FOXN3 had an inhibitory effect on the proliferation, migration, invasion and angiogenesis of OVCAR3 cells, while its knockdown exhibited an opposite effect in A2780 cells. By inoculation of FOXN3-overexpressing cells into nude mice, tumorigenesis assay demonstrated that FOXN3 could delay the growth of ovarian cancer cells in vivo. The interaction between FOXN3 and RPS15A was preliminarily explored via dual-luciferases assay and ChIP. FOXN3 was confirmed to bind to the promoter (at − 1588/− 1581 and − 1476/− 1467) of gene RPS15A and inhibit its transcriptional expression. We further found that overexpression of RPS15A diminished the inhibition of FOXN3 on ovarian cancer cell malignant behaviors. These findings indicate that FOXN3 negatively regulates the expression of RPS15A and thus suppresses the progression of ovarian cancer.

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Acknowledgements

This study was funded by the National Natural Science Foundation of China (Grant No. 82001846) and the 345 Talent Project of Shengjing Hospital of China Medical University.

Funding

This study was funded by the National Natural Science Foundation of China (Grant No. 82001846) and the 345 Talent Project of Shengjing Hospital of China Medical University.

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Authors and Affiliations

  1. Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China

    Hua Yang

  2. Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China

    Mingyu Li

  3. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China

    Yue Qi

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  1. Hua Yang
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Correspondence to Yue Qi.

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All clinical studies and animal studies were approved by the ethics committee of Shengjing Hospital of China Medical University. All animal experiments were performed by the Guide for the Care and Use of Laboratory Animals. The clinical studies in human were conducted in accordance with the principles of the Helsinki Declaration.

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Yang, H., Li, M. & Qi, Y. FOXN3 inhibits the progression of ovarian cancer through negatively regulating the expression of RPS15A. Human Cell 36, 1120–1134 (2023). https://doi.org/10.1007/s13577-023-00876-9

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