VEZF1 inhibits ovarian cancer cell ferroptosis and acts as an oncogene via the miR-545-3p/ PLAG1 axis

Sep 23, 2026

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Ovarian cancer remains a lethal malignancy, and ferroptosis is explored as a potential route to limit tumor growth. The study investigates the role of vascular endothelial zinc finger 1 (VEZF1) in ovarian cancer cell ferroptosis and seeks therapeutic targeting opportunities. VEZF1, miR-545-3p, and PLAG1 expressions were measured in cell lines, then VEZF1 was silenced to assess proliferation and ferroptosis markers. Mechanistic validation confirms a VEZF1-driven miR-545-3p/PLAG1 axis.

LanguageEnglish

CategoryHealthcare

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Abstract

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Shi et al. Hereditas (2026) 163:65 [https://doi.org/10.1186/s41065-026-00672-z](https://doi.org/10.1186/s41065-026-00672-z) Hereditas RESEARCH Open Access VEZF1 inhibits ovarian cancer cell ferroptosis and acts as an oncogene via the miR-545-3p/ PLAG1 axis Wei Shi1,2, Weiwei Feng2, Jing Wan2 and Xiao-Ping Wan1* Abstract Background Ovarian cancer (OC) is a fatal carcinoma for women. This study attempts to explore the role of vascular endothelial zinc finger 1 (VEZF1) in OC cell ferroptosis, thereby finding a new target for OC treatment. Methods Expressions of VEZF1, miR-545-3p and PLAG1 in HOSE cell line and OC cell lines were determined by RT-qPCR and western blot analysis. After VEZF1 was silenced in cells, cell proliferation was examined, contents of ROS, MDA, Fe2+, GSH were detected, and expressions of ACSL4 and GPX4 were tested. Afterwards, the binding relation between VEZF1 and miR-545-3p and between miR-545-3p and PLAG1 were verified. Functional rescue assays were formulated to validate the role of miR-545-3p knockdown or PLAG1 overexpression in OC cell ferroptosis. Results VEZF1 was overexpressed in OC, and VEZF1 silencing reduced cell proliferation, elevated levels of ROS, MDA, Fe2+, inactivated levels of GSH and GPX4, and enhanced ACSL4 expression. Functionally, VEZF1 transcriptionally inhibited miR-545-3p, and miR-545-3p targeted and inhibited PLAG1 . miR-545-3p knockdown or PLAG1 overexpression could reverse the effect of VEZF1 silencing on OC cell ferroptosis. Conclusion VEZF1 was overexpressed in OC and it limited OC cell ferroptosis by transcriptionally inhibiting miR- 545-3p and elevating PLAG1 expression. Keywords Ovarian cancer, High glucose, Ferroptosis, VEZF1, miR-545-3p, PLAG1 *Correspondence: Xiao-Ping Wan [XiaopingWann@163.com](XiaopingWann@163.com) 1Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, No.550 Hu’nan Road, Shanghai 200092, China 2Department of Gynaecology and Obstetrics, School of Medicine, The International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, Shanghai 200030, China Introduction Ovarian cancer (OC) remains one of the most lethal gynecological malignancies, with high recurrence ratesand poor overall survival due to its insidious onset and frequent diagnosis at advanced stages [1]. Family history of gynecological diseases, excessive hormone administration, diabetes, unhealthy lifestyle, and overweight are major reasons for OC development [2]. Although cytoreductive surgery, platinum-based chemotherapy, and targeted therapies (e.g., PARP inhibitors and anti-angiogenic agents) are standard treatments, drug resistance and toxicity severely limit their long-term efficacy [3]. Elucidating the molecular mechanisms driving OC progression is therefore essential for identifying novel therapeutic © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The)[. The](http://creativecommons.org/licenses/by/4.0/. The)[ ](http://cre

FAQs

What is the main focus regarding VEZF1 in ovarian cancer cells?

The study focuses on how VEZF1 influences ovarian cancer cell ferroptosis and determines whether VEZF1 functions as an oncogene through a molecular axis.

How were VEZF1, miR-545-3p, and PLAG1 expressions evaluated?

Expressions were determined using RT-qPCR and western blot analysis in HOSE and ovarian cancer cell lines.

What did VEZF1 silencing show about ferroptosis-related markers?

VEZF1 silencing reduced cell proliferation and increased ROS and MDA, elevated Fe2+, reduced GSH and GPX4 activity levels, and enhanced ACSL4 expression.

How does the miR-545-3p/PLAG1 axis connect VEZF1 to ferroptosis?

VEZF1 transcriptionally inhibits miR-545-3p, miR-545-3p targets and inhibits PLAG1, and miR-545-3p knockdown or PLAG1 overexpression reverses VEZF1-silencing effects on ferroptosis.

Sep 23, 2026

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