PSMB1 screened by CRISPR-CAS9 promoted breast cancer progression via PI3K-AKT-mTOR signaling

Breast cancer is a threat to women's health worldwide. Recent studies have focused on the role of differentially expressed genes in tumors. PSMB1 has been reported to play an important role in tumors, however, its role in breast cancer has not been well defined.

The CRISPR-CAS9 data was analyzed and intersected with Cox univariate analyzation to screen differentially expressed genes in breast cancer. The prognosis of PSMB1 was predicted by Kaplan-Meier plotter, and the related major pathways were analyzed through GO analysis and GSEA. PSMB1-related gene mutations and Tumor microenvironment characteristics were analyzed. The expression of PSMB1 in breast cancer tissues and cells were determined by RT-qPCR and IHC. MTT, colony formation assay, EdU, Transwell, wound healing assay and cell cycle assay were performed to observe its function in vitro. The western blot was conducted to detect its regulation on EMT markers and key proteins in PI3K pathway.

In this study, PSMB1 was screened by CRISPR-Cas9 and identified to be upregulated in breast cancer samples. By further analysis, PSMB1 was found to be involved in tumor-related biological process and correlated with worse prognosis in breast cancer patients. In vitro experiments verified that downregulation of PSMB1 could inhibit the malignant phenotype of breast cancer cells. The western blot showed that si-PSMB1 significantly decreased the expression of key proteins and their phosphorylation form in PI3K-AKT-mTOR signaling.

si-PSMB1 inhibited breast cancer cell proliferation, invasion and migration probably by targeting PI3K-AKT-mTOR signaling, which brings innovative mechanisms for breast cancer regulation and emerging ideas for therapeutic strategies.