@Article{or.2023.028256,
AUTHOR = {SHUIZHONG CEN, XIAOJIE PENG, JIANWEN DENG, HAIYUN JIN, ZHINAN DENG, XIAOHUA LIN, DI ZHU, MING JIN, YANWEN ZHU, PUSHENG ZHANG, YUNFENG LUO, HONGYAN HUANG},
TITLE = {The role of AFAP1-AS1 in mitotic catastrophe and metastasis of triple-negative breast cancer cells by activating the PLK1 signaling pathway},
JOURNAL = {Oncology Research},
VOLUME = {31},
YEAR = {2023},
NUMBER = {3},
PAGES = {375--388},
URL = {http://www.techscience.com/or/v31n3/52820},
ISSN = {1555-3906},
ABSTRACT = {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 <i>AFAP1-AS1</i> plays a crucial role in various tumors, but whether <i>AFAP1-AS1</i> 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 <i>AFAP1-AS1</i> in the TNBC patient cohort and primary cells by <i>in situ</i> hybridization (ISH), northern blot, fluorescent <i>in situ</i> 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 <i>AFAP1-AS1</i> by transwell, apoptosis, immunofluorescence (IF) and patient-derived xenograft (PDX) models <i>in vitro</i> and <i>in vivo</i>. We found that <i>AFAP1-AS1</i> promoted TNBC primary cell survival by inhibiting mitotic catastrophe and increased TNBC primary cell growth, migration and invasion. Mechanistically, <i>AFAP1-AS1</i> activated phosphorylation of the mitosis-associated kinase PLK1 protein. Elevated levels of <i>AFAP1-AS1</i> in TNBC primary cells increased PLK1 pathway downstream gene expression, such as CDC25C, CDK1, BUB1 and TTK. More importantly, <i>AFAP1-AS1</i> increased lung metastases in a mouse metastasis model. Taken together, <i>AFAP1-AS1</i> functions as an oncogene that activates the PLK1 signaling pathway. <i>AFAP1-AS1</i> could be used as a potential prognostic marker and therapeutic target for TNBC.},
DOI = {10.32604/or.2023.028256}
}