Amino-Modified Magnetic Nanoparticles Used in Exploring the Mechanism of CCL18-Induced H19 Upregulation that Promotes Breast Cancer Cell Invasion by Regulating the EZH2-Mediated Repression of E-Cadherin Expression

Abstract

The acceleration of Chemokine (C–C motif) ligand 18 (CCL18) and long noncoding RNA H19 expression is reportedly closely associated with breast cancer (BC) development and progression; however, the underlying mechanism and clinical value between CCL18 and H19 in BC remain unclear. Hence, this study aimed to examine the expression and function of CCL18 and H19 in BC tissues and cells by real-time polymerase chain reaction, immunohistochemistry, and other methods. We also detected the binding of EZH2 and other proteins to H19 through nanomagnetic bead immunoprecipitation and analyzed the roles of CCL18 and H19 in BC progression and their underlying mechanisms. Both CCL18 and H19 were upregulated in BC tissues and cell lines. High expression of CCL18 and EZH2 was closely associated with short survival in patients with BC. CCL18 or H19 silencing can prohibit BC cell invasion. Moreover, CCL18 accelerated the invasiveness of BC cells dose-dependently, and its expression was positively related to H19 expression in BC tissues. CCL18 enhanced H19 expression, while H19 knockdown partially ameliorated CCL18-induced BC cell invasiveness. Mechanistically, H19 can directly bind with EZH2 and mediate its accumulation at the promoter region of E-cadherin genes, consequently inhibiting E-cadherin expression. In conclusion, CCL18 promotes BC progression by enhancing H19 expression, and H19 overexpression suppresses E-cadherin expression via EZH2-mediated inhibition. Thus, this study describes a potential biomarker for the diagnosis, prognosis, and treatment of BC.