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, Ncadherin 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.

TP73-AS1 as a predictor of clinicopathological parameters and prognosis in human malignancies: a meta and bioinformatics analysis

“…In the female reproductive system, Wang et al [ 17 ] demonstrated that TP73‐AS1 facilitated cell proliferation and the metastasis of ovarian cancer through its regulation of MMP2 and MMP9 expression. In addition, TP73-AS1 boosted cell proliferation, invasion, and migration, and functioned as a ceRNA with miR-200a to prevent binding of TFAM, dampening the TP73-AS1/miR-200a/ZEB1 and TP73-AS1/miRNA-125a-3p/ metadherin axis in breast cancer [ 18 , 19 , 31 ]. Zhang et al [ 20 ] also reported that the upregulation of TP73-AS1 promotes the tumorigenesis of cervical cancer by promoting CCND2 through the suppression of miR-607 expression.…”

TP73-AS1 as a Predictor of Clinicopathological Parameters and Prognosis in Human Malignancies: A Meta and Bioinformatics Analysis

“…In the female reproductive system, Wang et al [17] demonstrated that TP73-AS1 facilitated cell proliferation and the metastasis of ovarian cancer through its regulation of MMP2 and MMP9 expression. In addition, TP73-AS1 boosted cell proliferation, invasion, and migration, and functioned as a ceRNA with miR-200a to prevent binding of TFAM, dampening the TP73-AS1/miR-200a/ZEB1 and TP73-AS1/miRNA-125a-3p/metadherinaxis in breast cancer [18,19,31]. Zhang et al [20] also reported that the upregulation of TP73-AS1 promotes the tumorigenesis of cervical cancer by promoting CCND2 through the suppression of miR-607 expression.…”

LncRNA TP73‐AS1 promotes nasopharyngeal carcinoma progression through targeting miR-342-3p and M2 polarization via exosomes

“…Raw data were analyzed using ΔΔCT method [ 24 ]. The primer information was as following: GAPDH: 5′-AAGGCTGAGAATGGGAAAC-3′ (Forward) and 5′-TTCAGGGACTTGTCATACTTC-3′ (Reverse), U6: 5′-GCTTCGGCAGCACATATACTAAAAT-3′ (Forward) and 5′-CGCTTCACGAATTTGCGTGTCAT-3′ (Reverse); miRNA-342-3p: 5′-GTGCTATCTGTGATTGAGGGA-3′ (Forward) and 5′-CGGGTGCGATTTCTGTG-3′ (Reverse); TP73-AS1: 5′-CCGGTTTTCCAGTTCT TGCAC-3′ (Forward) and 5′-GCCTCACAGGGAAACTTCATGC-3′ (Reverse) [ 25 ].…”