The role of PCSK9 in regulating the biological function and ferroptosis sensitivity of prostate cancer cells

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Author: WANG Shichun SHI Minghui WANG Danqi XI Shu CUI Jinlong LIU Shuyan  YUAN Shuai  JIN Yinghui

Affiliation: WANG Shichun, SHI Minghui, WANG Danqi, XI Shu, CUI Jinlong, LIU Shuyan,[yuanshuai021@whu.edu.cn]YUAN Shuai,[jinyinghui0301@163.com]JIN Yinghui

Keywords: Prostate cancer Proprotein convertase subtilisin/kexin type 9 Proliferation Migration Invasion Ferroptosis

DOI: 10.12173/j.issn.1005-0698.202411088

Reference: WANG Shichun, SHI Minghui, WANG Danqi, XI Shu, CUI Jinlong, LIU Shuyan, YUAN Shuai, JIN Yinghui. The role of PCSK9 in regulating the biological function and ferroptosis sensitivity of prostate cancer cells[J]. Yaowu Liuxingbingxue Zazhi, 2025, 34(3): 282-292. DOI: 10.12173/j.issn.1005-0698.202411088.[Article in Chinese]  Copied

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Abstract

Objective To investigate the biological function of the proprotein convertase subtilisin/kexin type 9 (PCSK9) in prostate cancer (PCa) and its effect on ferroptosis sensitivity

Methods Bioinformatics was used to analyze the relationship between the expression of PCSK9 and the prognosis of prostate cancer. The expression of PCSK9 in PCa cell lines were detected using RT-qPCR. PCa cells with PCSK9 knockdown were constructed using siRNA, and the The effect of PCSK9 on cell proliferation, migration, and invasion were detected using CCK-8 assays and Transwell assays. The Cancer Therapeutics Response Portal (CTRP) was employed to investigate the correlation between PCSK9 and ferroptosis drug sensitivity, and PCa cells with PCSK9 knockdown were treated with the ferroptosis inducer (RSL3) to detect the sensitivity to ferroptosis.

Results Bioinformatics showed low expression of PCSK9 had longer disease specific survival (P<0.05). The results of the in vitro experiments showed that PCSK9 knockdown significantly inhibited the proliferation, migration, and invasion of PCa cells (P<0.001). Furthermore, CTRP analysis showed that cellular sensitivity to ferroptosis inducers correlated with the expression level of PCSK9. PCSK9 knockdown cells exhibited higher sensitivity to the ferroptosis inducer RSL3.

Conclusion Knockdown of PCSK9 inhibits the proliferation, migration, and invasion of PCa cells, and increases the sensitivity of cells to ferroptosis inducers. PCSK9 may provide new insights for the treatment of PCa.

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