Long non-coding RNA AFAP1-AS1 promotes tumor progression and invasion by regulating the miR-2110/Sp1 axis in triple negative breast cancer

Background: LncRNAs have been proved to be involved in the proliferation, apoptosis, invasion, migration and other pathological processes of triple negative breast cancer (TNBC). And the expression level of LncRNA AFAP1-AS1 in TNBC was found to be significantly higher than that in other subtypes and normal tissue samples, but the specific mechanism of LncRNA AFAP1-AS1 affecting the occurrence and development of TNBC needs to be revealed. Methods: Cell Counting Kit-8 assays, colony formation assays, wound-healing migration, transwell invasion assays and nude mouse xenograft assays were used to confirm the role of LncRNA AFAP1-AS1 in the proliferation, migration of TNBC cells in vitro and in vivo. Bioinformatics analyses, quantitative polymerase chain reaction (qRT-PCR), western blot, and dual-luciferase assays were performed to confirm the interaction between between LncRNA AFAP1-AS1, miR-2110 and Sp1. Results: In the present study, the silencing of AFAP1-AS1 and Sp1 or the upregulation of miR-2110 would result in the suppression of proliferation, migration and invasion of MDA-MB-231 and MDA-MB-468 cells in vitro as well as tumor growth in vivo. Mechanistically, the dual-luciferase reporter assay highlighted that AFAP1-AS1 functioned as a miR-2110 sponge to increase Sp1 expression. AFAP1-AS1 silencing led to a reduction in Sp1 mRNA and protein levels, which could be reverse by the joint transfection of miR-2110 inhibitor. Conclusions: Our findings demonstrated that AFAP1-AS1 acts as a miR-2110 sponge in TNBC cells, resulting in the regulation of Sp1 expression. And the AFAP1-AS1/miR-2110/Sp1 axis modulated the proliferation, migration and invasion of breast cancer cells and affected the tumorigenesis in mice.