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.

Keywords

• Breast cancer
• malignant progression
• miR‐125a
• MTDH
• TP73‐AS1