Ubiquitin-specific peptidase 53 suppresses the tumorigenesis of breast cancer cells and its related gene analysis

Background

Breast cancer (BC) remains the most common malignancy affecting women's health globally. Thus, elucidating the molecular mechanisms driving BC progression and identifying novel therapeutic targets is imperative. Ubiquitin-specific peptidase 53 (USP53) is a deubiquitinating enzyme reported to exert tumor-suppressive effects in several types of cancers. However, USP53 has been poorly studied in BC.

Methods

Based on the TCGA database and GTEx transcriptome data, differentially expressed genes in BC were screened, and the relationship between USP53 expression and BC characteristics and prognosis were analyzed. qRT-PCR, Western blot, and immunohistochemistry determined USP53 expression. After transfection, BC cells’ proliferation, migration, and invasion were assessed using CCK-8 and Transwell assay. A subcutaneous xenograft tumor model in nude mice was used to evaluate the in vivo effect of USP53. Besides, USP53 expression-associated immune cells were screened using the Cibersort package.

Results

USP53 expression was reduced in BC patients and showed potential diagnostic significance. Functionally, overexpressing USP53 inhibited BC cell proliferation, migration, and invasion, while silencing it promoted these malignant behaviors. In vivo, tumors derived from USP53-overexpressing cells grew more slowly and exhibited lower Ki67 expression. Additionally, we found that Tcm, T helper cells, Mast cells, and Eosinophils were positively associated with USP53 expression, whereas NK CD56dim cells and TReg were negatively associated with USP53 expression.

Conclusions

Together, we proved that USP53 was down-regulated in BC and weakened the malignant progression of BC cells both in vitro and in vivo. USP53 was also associated with a variety of immune cells. Our study suggested that USP53 may be a novel target for BC therapy.