SOX2-OT induced by PAI-1 promotes triple-negative breast cancer cells metastasis by sponging miR-942-5p and activating PI3K/Akt signaling.
Wenwen ZhangShuofei YangDatian ChenDaolu YuwenJuan ZhangXiaowei WeiXin HanXiaoxiang GuanPublished in: Cellular and molecular life sciences : CMLS (2022)
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.
Keyphrases
- signaling pathway
- pi k akt
- cell cycle arrest
- induced apoptosis
- transcription factor
- stem cells
- cell proliferation
- cell death
- epithelial mesenchymal transition
- long non coding rna
- poor prognosis
- breast cancer cells
- randomized controlled trial
- systematic review
- ejection fraction
- cell therapy
- long noncoding rna
- oxidative stress
- endoplasmic reticulum stress
- drug induced
- climate change
- endothelial cells
- prognostic factors
- risk assessment
- protein kinase
- patient reported outcomes