Knockdown of long non-coding RNA TP73-AS1 suppresses triple negative breast cancer cell vasculogenic mimicry by targeting miR-490-3p/TWIST1 axis

Abstract

Triple negative breast cancer (TNBC) is among the most clinically aggressive subtypes of breast cancer. Despite the availability of new drugs, patients suffering TNBC bear disheartening prognosis. Vasculogenic mimicry (VM) is a malignant tumor specific non-endothelial vascular network, which provide oxygen and nutrients to tumor cells and facilitate tumor progression. Therefore targeting TNBC VM formation may contribute to tumor treatment. In this study, we found that long non-coding RNA TP73 antisense RNA 1 (TP73-AS1) was upregulated in VM positive TNBC tissues. Knockdown of TP73-AS1 suppressed TNBC cell line MDA-MB-231 cell VM formation in vitro. In addition, RNA immunoprecipitation assay and dual luciferase reporter assay showed that TP73-AS1 bound to miR-490-3p in a sequence-specific manner. miR-490-3p was downregulated in VM positive tissues and was involved in TP73-AS1-mediated MDA-MB-231 cell VM formation. Furthermore, TWIST1 was a target of miR-490-3p and participated in TP73-AS1/miR-490-3p-modulated MDA-MB-231 cell VM formation. Findings in this study may provide insight in TNBC management.

Keywords: TP73-AS1; TWIST1; Triple negative breast cancer; Vasculogenic mimicry; miR-490-3p.