Long-chain noncoding RNA LINC01569 upregulates filamin A-interacting protein 1-like to prevent metastasis of triple-negative breast cancer via sponging miR-300

Abstract

BACKGROUND: Long-chain noncoding RNA (lncRNA), LINC01569, is important for regulating the extracellular matrix, which affects cell migration. However, its involvement in the occurrence and development of triple-negative breast cancer (TNBC) remains unclear. OBJECTIVE: This study is aimed to investigate the role of LINC01569 on TNBC. METHODS: Online database was used for clinical data analysis. Cell viability and migration capability were monitored using cell counting kit-8 and transwell assays, respectively. Luciferase reporter assay and RNA pull-down were used to confirm the binding capability between noncoding RNAs and filamin A-interacting protein 1-like (FILIP1L). Western blotting was used to determine the protein content. RESULTS: Compared with normal breast tissue, LINC01569 was significantly reduced in patients with TNBC subtype, and LINC01569 expression gradually decreased with the progression of tumor stage. Patients with TNBC with high lncRNA LINC01569 levels had a better prognosis than did patients with low LINC01569 levels. LINC01569 overexpression inhibited the migration capability, whereas siRNA-mediated LINC01569 downregulation promoted the migration capability in TNBC cells. Using ENCORI and lncRNA SNP online databases, miR-300 was screened as the potential sponge of LINC01569. The binding of LINC01569 to miR-300 was confirmed using the dual-luciferase reporter and RNA pull-down assays. miR-300 was negatively correlated with LINC01569, and miR-300 mimics eliminated the anti-proliferation and anti-migration effects of LINC01569 on TNBC cells. Additionally, FILIP1L was further verified as the downstream target of miR-300. miR-300 mimics blocked LINC01569 upregulation-mediated elevation of FILIP1L. Importantly, the anti-tumor effects mediated by LINC01569 overexpression were abolished by miR-300 mimics and further restored by FILIP1L upregulation. CONCLUSIONS: LINC01569 was expressed at a low level in TNBC and could sponge miR-300 to promote FILIP1L expression, reducing the proliferation and metastasis capability of TNBC. Thus, LINC01569 might be a useful biomarker in the diagnosis and prognosis of metastatic TNBC.