Background: Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, always exhibits a poor prognosis due to high risk of early recurrence and distant metastasis. Long noncoding RNAs (lncRNAs) have been reported as crucial regulators in breast cancer. However, the functions and action mechanisms of lncRNA ST8SIA6-AS1 in TNBC are largely unknown. Methods: Quantitative real-time PCR and western blot assays were used to measure the expression levels of different genes and proteins. Cell proliferation ability was monitored by CCK-8, colony forming and flow cytometry assays. Wound healing and transwell assays were performed to evaluate cell migration and invasion. The regulatory mechanisms of ST8SIA6-AS1 in TNBC were confirmed by dual luciferase reporter and RIP assays. A mouse xenograft model was established to investigate the role of ST8SIA6-AS1 in TNBC tumor growth. Results: ST8SIA6-AS1 displayed a higher expression in TNBC cells. Silencing ST8SIA6-AS1 impaired cell proliferation, cell cycle progression, migration, and invasion in vitro, and slowed tumor growth in vivo. Mechanistically, ST8SIA6-AS1 could facilitate the expression of its target CDCA3 (cell division cycle associated protein 3) and inactivate the p53/p21 signaling by inhibiting miR-145-5p. Moreover, miR-145-5p exerted a tumor-suppressive activity by targeting CDCA3. The tumorsuppressive effects induced by ST8SIA6-AS1 knockdown were abated by the downregulation of miR-145-5p or the up-regulation of CDCA3. Conclusion: ST8SIA6-AS1 exerts an oncogenic role in TNBC by interacting with miR-145-5p to up-regulate CDCA3 expression and inactivate the p53/p21 signaling, highlighting ST8SIA6-AS1 as a promising molecular target to combat TNBC.
Esophageal squamous cell carcinoma (ESCC) is among the most malignant types of digestive malignant tumor. Metastasis and recurrence contribute poor prognosis of ESCC. However, the mechanism of ESCC metastasis remains unclear. Here, we found high levels of Gli3 and p-Gli3S664 in ESCC tissues, which contributed to promote metastasis of ESCC cells in vitro. Importantly, we verified that serine-arginine protein kinase 1 (SRPK1) bound to Gli3 and phosphorylated Gli3 at the ser 664 residue, which promoted migration, invasion, and EMT of ESCC cells. Additionally, we found that dihydroartemisinin (DHA) inhibited metastasis of ESCC cells by downregulating SRPK1-mediated phosphorylation of Gli3S664 in vitro and in vivo. Thus, our findings demonstrate that the SRPK1-p-Gli3S664 axis plays an important role in ESCC metastasis and DHA may be a candidate drug to prevent ESCC metastasis by targeting the SRPK1-p-Gli3S664 axis.
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