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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