1. SOX2-OT induced by PAI-1 promotes triple-negative breast cancer cells metastasis by sponging miR-942-5p and activating PI3K/Akt signaling
- Author
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Wenwen Zhang, Shuofei Yang, Datian Chen, Daolu Yuwen, Juan Zhang, Xiaowei Wei, Xin Han, and Xiaoxiang Guan
- Subjects
Pharmacology ,Class I Phosphatidylinositol 3-Kinases ,Triple Negative Breast Neoplasms ,Cell Biology ,Gene Expression Regulation, Neoplastic ,Cellular and Molecular Neuroscience ,MicroRNAs ,Cell Transformation, Neoplastic ,Cell Line, Tumor ,Plasminogen Activator Inhibitor 1 ,Molecular Medicine ,Humans ,RNA, Long Noncoding ,Neoplasm Metastasis ,Molecular Biology ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Triple-negative breast cancer (TNBC) has an aggressive biological behavior and poor outcome. Our published study showed that PAI-1 could induce the migration and metastasis of TNBC cells. However, the underlying mechanism by which PAI-1 regulates TNBC metastasis has not been addressed. Here, we demonstrated that PAI-1 is high expressed in TNBC and promotes TNBC cells tumorigenesis. Using microarray analysis of lncRNA expression profiles, we identified a lncRNA SOX2-OT, which is induced by PAI-1 and could function as an oncogenic lncRNA in TNBC. Mechanistic analysis demonstrated that SOX2-OT acts as a molecular sponge for miR-942-5p to regulate the expression of PIK3CA, ultimately leading to activating PI3K/Akt signaling pathway and promoting TNBC metastasis. Taken together, our findings suggest that SOX2-OT regulates PAI-1-induced TNBC cell metastasis through miR-942-5p/PIK3CA signaling and illustrate the great potential of developing new SOX2-OT-targeting therapy for TNBC patients.
- Published
- 2021