Knockdown of LncRNA-UCA1 Inhibits Breast Cancer Growth in Association with METTL14/miR-375/SOX12 Axis

Background Breast cancer is a malignant tumor with high incidence in females. Burgeoning studies have analyzed the relationship between long non-coding RNA (lncRNA) and breast cancer. However, the role of LncRNA UAC1 in the pathogenesis of breast cancer remains unclear. Methods LncRNA-UCA1 levels were detected in breast cancer tissues and cells while correlation between LncRNA-UCA1 expression and patient survival was analyzed by the Kaplan-Meier. The proliferation, invasion and apoptosis of cells were measured by CCK-8 assay, Transwell test and flow cytometry, respectively. Protein levels of apoptosis-related factors were assessed by Western blots. RIP test detected the combination of LncRNA-UCA1 and DNA methyltransferases whereas RNA pull-down test showed the interaction of DNA methyltransferases and LncRNA UCA1. Enrichment of DNA transferase of METTL14 promoter in T47D was assessed by ChIP. Interaction between miR-375 and SOX12 was confirmed via dual-luciferase reporter assay. Tumorigenesis was observed in vivo. Results LncRNA-UCA1 levels were increased in breast cancer and a high LncRNA-UCA1 level was a risk factor of the poor breast cancer prognosis. Silencing LncRNA-UCA1 inhibited the proliferation and invasion but promoted apoptosis of breast cancer cells. LncRNA-UCA1 recruited DNA methyltransferase to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. Low METTL14 levels were associated with stronger proliferation and invasion abilities, whereas weaker proliferation and invasion abilities were related to low LncRNA-UCA1 levels. METTL14 mediated the low expression of miR-375 by m6A modification in breast cancer. Conclusion Depleted LncRNA-UCA1 inhibited breast cancer growth by regulating the METTL14-miR-375-SOX12 axis in vitro and in vivo.