Pan Wang1, Wenju Chen1, Yaqiong Zhang1, Qianyi Zhong1, Zhaoyun Li1, Yichao Wang2,3. 1. Department of Laboratory Medicine, Taizhou Central Hospital, Taizhou, 318000, Zhejiang, China. 2. Department of Laboratory Medicine, Taizhou Central Hospital, Taizhou, 318000, Zhejiang, China. tzyyycw@sina.com. 3. Department of Clinical Laboratory Medicine, Taizhou Central Hospital (Taizhou University Hospital), No. 999 Donghai Road, Jiaojiang District, Taizhou, 318000, Zhejiang, People's Republic of China. tzyyycw@sina.com.
Abstract
OBJECTIVE: Breast cancer is one of the most common malignant and highly heterogeneous tumors in women. MicroRNAs (miRNAs), such as miR-1246, play important roles in various types of malignant cancers, including triple-negative breast cancer (TNBC). However, the biological role of miR-1246 in TNBC has not yet been fully elucidated. In this study, we studied the role of miR-1246 in the occurrence and development of TNBC and its mechanism of action. METHODS: Cell Counting Kit-8 (CCK-8), wound healing, and Transwell assays were performed to observe the effects of miR-1246 on TNBC cell proliferation, migration, and invasion, respectively. The expression of epithelial-mesenchymal transition (EMT) markers was detected by western blotting. Dual luciferase reporter assays were performed to determine whether DYRK1A is a novel target of miR-1246. In addition, an immunoprecipitation experiment was performed to verify the binding of DYRK1A to PGRN. Rescue experiments were performed to determine whether DYRK1A is a novel target of miR-1246 and whether miR-1246 suppresses the metastasis of breast cancer cells by targeting the DYRK1A/PGRN axis to prevent the epithelial-mesenchymal transition. RESULTS: Our results show that miR‑1246 suppresses the proliferation, migration, and invasion of TNBC cells, DYRK1A is a novel target of miR-1246 and Importin-8 mediated miR-1246 nuclear translocation. MiR‑1246 plays a suppressive role in the regulation of the EMT of TNBC cells by targeting DYRK1A. DYRK1A mediates the metastasis of triple-negative breast cancer via activation of the EMT. We identified PGRN as a novel DYRK1A-interacting protein. Overexpression of PGRN and DYRK1A promoted cell proliferation and migration of TNBC, but this effect was reversed by co-expression of miR-1246 mimics.DYRK1A and PGRN act together to regulate the occurrence and development of breast cancer through miR-1246. CONCLUSION: MiR-1246 suppresses the metastasis of breast cancer cells by targeting the DYRK1A/PGRN axis and preventing the epithelial-mesenchymal transition. The MiR-1246/DYRK1A/PGRN axis regulates TNBC progression, suggesting that MiR-1246 could be promising therapeutic targets for the treatment of TNBC.
OBJECTIVE: Breast cancer is one of the most common malignant and highly heterogeneous tumors in women. MicroRNAs (miRNAs), such as miR-1246, play important roles in various types of malignant cancers, including triple-negative breast cancer (TNBC). However, the biological role of miR-1246 in TNBC has not yet been fully elucidated. In this study, we studied the role of miR-1246 in the occurrence and development of TNBC and its mechanism of action. METHODS: Cell Counting Kit-8 (CCK-8), wound healing, and Transwell assays were performed to observe the effects of miR-1246 on TNBC cell proliferation, migration, and invasion, respectively. The expression of epithelial-mesenchymal transition (EMT) markers was detected by western blotting. Dual luciferase reporter assays were performed to determine whether DYRK1A is a novel target of miR-1246. In addition, an immunoprecipitation experiment was performed to verify the binding of DYRK1A to PGRN. Rescue experiments were performed to determine whether DYRK1A is a novel target of miR-1246 and whether miR-1246 suppresses the metastasis of breast cancer cells by targeting the DYRK1A/PGRN axis to prevent the epithelial-mesenchymal transition. RESULTS: Our results show that miR‑1246 suppresses the proliferation, migration, and invasion of TNBC cells, DYRK1A is a novel target of miR-1246 and Importin-8 mediated miR-1246 nuclear translocation. MiR‑1246 plays a suppressive role in the regulation of the EMT of TNBC cells by targeting DYRK1A. DYRK1A mediates the metastasis of triple-negative breast cancer via activation of the EMT. We identified PGRN as a novel DYRK1A-interacting protein. Overexpression of PGRN and DYRK1A promoted cell proliferation and migration of TNBC, but this effect was reversed by co-expression of miR-1246 mimics.DYRK1A and PGRN act together to regulate the occurrence and development of breast cancer through miR-1246. CONCLUSION: MiR-1246 suppresses the metastasis of breast cancer cells by targeting the DYRK1A/PGRN axis and preventing the epithelial-mesenchymal transition. The MiR-1246/DYRK1A/PGRN axis regulates TNBC progression, suggesting that MiR-1246 could be promising therapeutic targets for the treatment of TNBC.