USP34 regulates PIN1-cGAS-STING axis-dependent ferroptosis in cervical cancer via SUMOylation

Cervical cancer is a prevalent form of cancer in women, and the inhibition of ferroptosis has been shown to promote the progression of cervical cancer tumours. This study aimed to investigate the role of PIN1 in regulating ferroptosis in cervical cancer, focusing on its ability to modulate the cGAS-STING pathway and the potential involvement of USP34 as an upstream regulator of PIN1.

PIN1-overexpressing and PIN1-knockdown cell lines were constructed. In addition to activating p-STING via PIN1 knockdown and inhibiting p-STING via PIN1 overexpression, cell activity was evaluated via CCK8, EdU, transwell and flow cytometry assays. The expression of USP34, PIN1, cGAS, p-STING, and STING was analysed through qRT-PCR and immunofluorescence. Western blot analysis was used to detect the regulatory effects of USP34, PIN1, cGAS, p-STING, and STING, as well as SUMOylation. Ferroptosis was detected by ROS immunofluorescence, the mitochondrial membrane potential, and mitochondrial electron microscopy. Furthermore, PIN1-knockdown cells were used to construct xenograft tumours in BALB/c male nude mice, and the relevant verification experiments were performed in vivo.

PIN1 can increase the proliferation and invasion of cervical cancer cells by significantly inhibiting ferroptosis. The mechanism by which PIN1 promotes cancer is inhibition of the cGAS-STING pathway. Additionally, we found that USP34 could increase the expression of PIN1 via SUMOylation in cervical cancer cells.

This study confirmed that USP34 could upregulate PIN1 expression and SUMOylation, thereby inhibiting ferroptosis by suppressing the cGAS-STING pathway and in turn promoting the progression of cervical cancer.