Home HOME Neoplasma 2021 Neoplasma Vol.68, No.1, p.165–173, 2021

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Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

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Neoplasma Vol.68, No.1, p.165–173, 2021

Title: Tumor suppressor miR-424-5p abrogates ferroptosis in ovarian cancer through targeting ACSL4
Author: Lin-Lin Ma, Lin Liang, Dan Zhou, Shao-Wei Wang

Abstract: Ovarian cancer is the most lethal gynecological cancer. In spite of recent advances, clinical outcomes remain poor, urgently needing novel therapeutic approaches. Growing evidence indicates that microRNAs play crucial roles in ovarian carcinogenesis and progression and that ferroptosis serves as a novel tumor suppressor. However, the molecular mechanisms of miRNA-mediated ferroptosis regulation in ovarian cancer are still largely unknown. In the present study, we show that miR-424-5p negatively regulates ferroptosis by directly targeting ACSL4 in ovarian cancer cells. Upregulation of miR-424-5p suppressed ACSL4 by directly binding to its 3'-UTR, which subsequently reduced erastin- and RSL3-induced ferroptosis. Meanwhile, knockdown of miR-424-5p increased the sensitivity of ovarian cancer cells to erastin and RSL3. Furthermore, ACSL4 was upregulated in ovarian cancer tissues, and high ACSL4 expression predicted worse prognosis and sensitized ovarian cancer cells to erastin- and RSL3-induced ferroptosis. Importantly, decreases in lipid peroxides and ferroptotic cell death mediated by miR-424-5p could be abrogated by ACSL4 overexpression. Taken together, our findings demonstrate that miR-424-5p regulates ferroptosis by targeting ACSL4 in ovarian cancer cells and suggest a potential therapeutic approach for ovarian cancer.

Keywords: ovarian cancer; ACSL4; miR-424-5p; ferroptosis
Published online: 08-Oct-2020
Year: 2021, Volume: 68, Issue: 1 Page From: 165, Page To: 173

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