Upregulation of lncRNA SPINT1-AS1 by miR-200c/ZEB1 axis inhibits metastasis of breast cancer cells

Background Breast cancer is the most frequent and lethal malignancy among females worldwide. Metastasis crucially affects breast cancer-related deaths. Long noncoding RNAs (lncRNAs) are known to perform a crucial function in the regulation of biological processes in a variety of malignancies. The aim of this study was to evaluate the unidentified function played by the lncRNA SPINT1-AS1 and the relevant mechanism in the modulation of breast cancer-related metastasis. Methods Techniques such as immunohistochemistry (IHC) staining, western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence (IF) were applied to evaluate RNA and protein expression profiles. In vitro Transwell and wound healing tests, as well as in vivo lung metastasis experiments, were conducted to validate the cell's ability to invade and migrate. To identify the transcription factors that are involved in lncRNA SPINT1-AS1 interactions, the Chromatin Immunoprecipitation(ChIP) and dual-luciferase reporter assays were carried out. Finally, the role of lncRNA SPINT1-AS1 was evaluated in patients with breast cancer. Results lncRNA SPINT1-AS1 and miR-200c showed low levels of expression in breast cancer cell lines. Furthermore, the overexpression of lncRNA SPINT1-AS1 or miR-200c in the cell lines decreased the tumor cell invasion. Mechanistically, miR-200c induced the overexpression of the lncRNA SPINT1-AS1 via the mechanism of causing zinc finger E-box-binding homeobox members 1 (ZEB1) to bind directly to the promoter DNA of the lncRNA SPINT1-AS1. The miR-200c mediated upregulation of the lncRNA SPINT1-AS1 suppressed breast cancer cell metastasis via the STAT3 signaling pathway. Conclusion lncRNA SPINT1-AS1, which was up-regulated by the miR-200c/ZEB1 axis, performs a crucial function in inhibiting metastasis of breast cancer cells via the Phosphorylation-signal transducer and activator of transcription 3(p-STAT3) pathway and can be a novel prognostic and treatment target for the disease.