USP22 Facilitates Cervical Cancer Progression via Deubiquitinating and Stabilizing IRAK1 to Activate NF ‐ κB Signaling

Cervical cancer remains one of the most commonly diagnosed malignancies among women worldwide. Although USP22 is known to be involved in tumor progression, its specific function in cervical cancer remains unclear. This study explored the biological significance of USP22 and the mechanism by which it regulates cervical cancer progression. Through bioinformatic analysis, we identified that USP22 expression was significantly upregulated in cervical cancer tissues and was associated with proliferative potential. Single-cell RNA sequencing analysis revealed high USP22 expression in malignant epithelial cells, and USP22 expression was associated with the differentiation potential of cervical cancer cells. Moreover, USP22 deficiency suppressed cervical cancer cell proliferation, triggered cell cycle arrest in G0/G1, accelerated apoptosis, and inhibited migration and invasion. Mechanistically, USP22 bound to and deubiquitinated IRAK1, thereby preventing its proteasomal degradation and maintaining NF-κB pathway activation. USP22 deficiency significantly suppressed xenograft tumor growth and inhibited expression of the proliferation marker Ki67. Furthermore, IRAK1 overexpression abolished the suppressive effects of USP22 deficiency on cervical cancer cell growth and stemness. Collectively, this study provides evidence that USP22 regulates NF-κB signaling pathway by deubiquitinating and stabilizing IRAK1, suggesting that the USP22/IRAK1/NF-κB axis is a promising target for developing novel therapeutic strategies in cervical cancer.