The role of AFAP1-AS1 in mitotic catastrophe and metastasis of triple-negative breast cancer cells by activating the PLK1 signaling pathway.

Triple-negative breast cancer (TNBC) is characterized by fast growth, high metastasis, high invasion, and a lack of therapeutic targets. Mitosis and metastasis of TNBC cells are two important biological behaviors in TNBC malignant progression. It is well known that the long noncoding RNA plays a crucial role in various tumors, but whether is involved in the mitosis of TNBC cells remains unknown. In this study, we investigated the functional mechanism of AFAP1-AS1 in targeting Polo-like Kinase 1 (PLK1) activation and participating in mitosis of TNBC cells. We detected the expression of in the TNBC patient cohort and primary cells by hybridization (ISH), northern blot, fluorescent hybridization (FISH) and cell nucleus/cytoplasm RNA fraction isolation. High AFAP1-AS1 expression was negatively correlated with overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS) and recurrence-free survival (RFS) in TNBC patients. We explored the function of by transwell, apoptosis, immunofluorescence (IF) and patient-derived xenograft (PDX) models and . We found that promoted TNBC primary cell survival by inhibiting mitotic catastrophe and increased TNBC primary cell growth, migration and invasion. Mechanistically, activated phosphorylation of the mitosis-associated kinase PLK1 protein. Elevated levels of in TNBC primary cells increased PLK1 pathway downstream gene expression, such as CDC25C, CDK1, BUB1 and TTK. More importantly, increased lung metastases in a mouse metastasis model. Taken together, functions as an oncogene that activates the PLK1 signaling pathway. could be used as a potential prognostic marker and therapeutic target for TNBC.