Apolipoprotein L3 inhibits breast cancer proliferation and modulates cell cycle via the P53 pathway.

Abstract

Background: Breast cancer is the second most common cause of cancer-related mortality globally. Apolipoprotein L3 (APOL3), a member of the apolipoprotein family, has been implicated in the pathogenesis of cardiovascular diseases. Nevertheless, the functions and underlying mechanisms of APOL3 in breast cancer have yet to be elucidated. Methods: The patient data were sourced from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry (IHC) assays were used to assess expression of APOL3. Cell proliferation rates were determined by Cell Counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was used to examine cell cycle distribution. Western blotting was conducted to investigate the expression of cell cycle related proteins. A xenograft model was used to evaluate the effect of APOL3 in vivo. APOL3-binding proteins were identified through mass spectrometry, co-immunoprecipitation (CO-IP) assay and immunofluorescence assay. Results: APOL3 expression was significantly downregulated in breast cancer, and its low expression was correlated with poor prognostic outcomes. Overexpression of APOL3 suppressed breast cancer cell proliferation, induced cell cycle disruption. Conversely, knockdown of APOL3 promoted cell proliferation. In vivo animal experiments demonstrated that APOL3 overexpression can inhibit tumor proliferation. Mass spectrometry, CO-IP and immunofluorescence assay confirmed the interaction between APOL3 and Y-box binding protein 1 (YBX1). Furthermore, YBX1 knockdown following APOL3 knockdown mitigated the enhanced proliferation. These results provide new ideas for clinically targeting APOL3 to inhibit proliferation in breast cancer. Conclusions: Our findings indicate that APOL3 inhibits breast cancer cell proliferation and cell cycle modulating P53 pathway through the interaction of YBX1.