ISG 15 is associated with cervical cancer development

Cervical cancer (CC) is a complex disease. Many factors contribute to the tumourigenesis and progression of CC neoplasms. Here, we analysed transcriptomic differences and simulated tumour progression to explore the pathogenesis of CC. RNA-seq was performed to analyse the transcriptomic differences among normal tissue (NC), paracarcinoma tissue (TP), and primary tumour tissue (TT). Pseudo-time analysis was performed to simulate tumour progression. RT-qPCR and immunohistochemistry were used to analyse the expression of ISG15. Cell proliferation, wound healing, and Transwell assays were used to verify the effect of ISG15 on HeLa cells. The RT-qPCR and immunohistochemistry results indicated that ISG15 had significantly higher expression in TT. We observed an increasing trend of ISG15 expression from NC to TP to TT, which suggests that elevated expression of ISG15 was closely associated with malignant evolution in CC tissues. HeLa cell experiments showed that ISG15-siRNA inhibited cell proliferation and invasion. Our study verifies that ISG15 is upregulated in and positively associated with the development of CC. ISG15 may act as an oncogene in the tumourigenesis of CC. The experiment was performed by comparative sequencing analysis using RNA-seq from TT, TP(2 cm≤TP≥0.5 cm from the tumour tissue), and NC(≥2 cm away from the tumour tissue) samples collected from 14 CC patients who underwent surgery at the People’s Hospital of Shanghai Pudong New District from January 2019 to June 2020. All patients had CC at stages IB1-IIA2 (based on the Criteria for Clinical Staging of Cervical Carcinoma 2018 Modified Version of the International Federation of Gynecology and Obstetrics [FIGO]) and underwent wide hysterectomy and lymphadenectomy in the pelvic cavity.