TRIM21 promotes tumor progression and cancer stemness in cervical squamous cell carcinoma

Abstract

Background: The ubiquitin ligase family member triplex motif protein 21 (TRIM21), which is involved in the proliferation, metastasis, and selective death of tumor cells, is crucial in the ubiquitination of a number of tumor marker proteins. As research progresses, more studies demonstrate that TRIM21 expression levels can be used to predict cancer prognosis. However, it is unclear how exactly TRIM21 contributes to cervical squamous carcinoma.

Methods: Immunohistochemistry, Western Blot, and q-PCR were utilized to determine the expression level of TRIM21 in 113 patients with CESC removed by stage I surgery at Xijing Hospital from 2018 to 2023 using paraffin-embedded tumor tissues and 12 pairs of fresh tumor tissues and their paracancerous tissues. Log-rank analysis using SPSS 23.0 was performed for prognosis and survival analysis using univariate/multifactorial analysis. CCK-8, wound-healing and Scratch assay verified that TRIM21 promoted cell proliferation, migration and invasion. The effect of overexpression and knockdown of TRIM21 on tumor stemness was examined using sphere-forming assay and Western Blot. Finally, we constructed a xenograft model to observe the effect of TRIM21 on tumorigenesis in Si Ha cell lines in vivo.

Results: TRIM21 expression is greater in CESC tissues than in paracancerous tissues, according to immunohistochemical data. Similarly, at the protein and mRNA levels, we verified this conclusion using Western-Blotting and q-PCR. Prognostic and OS analysis showed that TRIM21 expression levels are associated with individual prognostic factors. CCK-8, Wound healing, Transwell, and Sphere-forming tests all demonstrated that TRIM21 overexpression enhances Ca Ski cell proliferation, migration, invasion, and stemness. TRIM21 knockdown in Si Ha inhibited tumor cell proliferation, migration, invasion, and stemness. The experimental results of xenograft models demonstrated that TRIM21 knockdown in Si Ha cells inhibited tumor development.

Conclusion: TRIM21 is a poor predictor of prognosis for cervical squamous cell carcinoma and might open up new avenues for investigation into therapeutic targets.

Keywords: Cancer stemness; Cervical squamous cell carcinoma; TRIM21; Tumor progression.