MicroRNA-124-3p.1 promotes cell proliferation through Axin1-dependent Wnt signaling pathway and predicts a poor prognosis of triple-negative breast cancer

Abstract

Background: Triple-negative breast cancer (TNBC) is one subtype of breast cancer, which is characterized by an aggressive disease. It is commonly accompanied with extremely poor prognosis because of no available molecularly targeted therapy. Thus, understanding the detailed molecular mechanisms of TNBC is urgently needed. Methods: The levels of Axis inhibition protein 1 (Axin1), Cyclin D1, c-Myc, and miR-124-3p.1 were measured by quantitative real-time PCR (qRT-PCR). Furthermore, the breast cancer cell proliferation was measured by CCK-8 assay, colony formation assays, and EdU staining. Xenograft model was used to show the tumor genesis of breast cancer cells. The regulatory function of miR-124-3p.1 on Wnt/β-catenin signaling activation through directly targeting Axin1 was proven using qRT-PCR, Western blot analysis, and dual-luciferase reporter assay. To further assess the clinical significance of miR-124-3p.1 in the prognosis of breast cancer patients, we performed Kaplan-Meier survival analysis and log-rank tests. Results: miR-124-3p.1 expression was elevated in advanced TNBC patients, and high miR-124-3p.1 predicts poor overall survival in TNBC patients. Further data showed that miR-124-3p.1 downregulation diminished, while miR-124-3p.1 upregulation increased the growth of TNBC cells in vitro and in vivo. Finally, we proved that miR-124-3p.1 exerted its function via targeting tumor suppressor gene Axin1 and activating the Wnt signaling pathway. Conclusion: In summary, all the results demonstrate that miR-124-3p.1 promotes TNBC cell growth by controlling Axin1, suggesting that targeting miR-124-3p.1 might offer an effective therapeutic strategy for TNBC in the future.