Knockdown of long noncoding RNA TP73-AS1 suppresses the malignant progression of breast cancer cells in vitro through targeting miRNA-125a-3p/metadherin axis

Abstract

Background: TP73 antisense RNA 1 (TP73-AS1) is a long noncoding RNA which has been shown to be involved in the progression of multiple malignant tumors. Previous studies have demonstrated the oncogenic role of TP73-AS1 in breast cancer. However, its molecular mechanism remains largely unknown in breast tumorigenesis. Methods: Expression of TP63-AS1, miRNA-125a-3p (miR-125a) and metadherin (MTDH) was detected by real-time quantitative PCR and western blotting. The malignancy was evaluated by cell counting kit 8 (CCK-8), transwell assays, flow cytometry and western blotting. The target binding was confirmed by dual luciferase reporter assay. Xenograft tumor model was performed to detect tumor growth in vivo. Results: Expression of TP73-AS1 was higher in breast cancer tissues and cell lines. Biologically, its knockdown could promote cell apoptosis rate, and inhibit proliferative capacity, migration and invasion ability in HCC-70 and MB231 cells, accompanied with higher cleaved caspase 3 level and lower Ki67, N-cadherin and Vimentin level. Moreover, TP73-AS1 downregulation restrained the tumor growth of HCC-70 cells in vivo. Mechanically, TP73-AS1 functioned as a molecular “sponge” for miR-125a to modulate MTDH, a downstream target of miR-125a. Intriguingly, both miR-125a overexpression and MTDH silencing exerted a tumor-suppressive effect in the malignant progression of HCC-70 and MB231 cells, which was counteracted by TP73-AS1 upregulation and miR-125a downregulation, respectively. Conclusion: Knockdown of TP73-AS1 inhibited cell proliferation, migration and invasion, but facilitated apoptosis in breast cancer cells in vitro through targeting miR-125a and upregulating MTDH, suggesting a novel TP73-AS1/miR-125a/MTDH pathway in the malignant progression of breast cancer.