Long Noncoding RNA <i>NEAT1</i> Promotes the Progression of Breast Cancer by Regulating miR-138-5p/ <i>ZFX</i> Axis

Abstract

<b><i>Background:</i></b> Growing evidence demonstrated that long noncoding RNAs (lncRNAs) were involved in the progression of diverse cancers, including breast cancer (BC). Recent studies indicated that lncRNA nuclear enriched abundant transcript 1 (<i>NEAT1</i>) was overexpressed and facilitated tumor processes in many cancers. Nevertheless, the underlying mechanism of <i>NEAT1</i> in regulating BC progression is still largely unknown. <b><i>Materials and Methods:</i></b> The abundance of <i>NEAT1</i>, microRNA-138-5p (miR-138-5p), and zinc finger protein X-linked (<i>ZFX</i>) was assessed by quantitative real-time polymerase chain reaction. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and transwell assay were utilized to evaluate cell proliferation, apoptosis, migration, and invasion, respectively. Western blot analysis was applied to detect the protein expression of CyclinD1, Bax, E-cadherin, and <i>ZFX</i>. The interaction between miR-138-5p and <i>NEAT1</i> or <i>ZFX</i> was predicted by starBase v3.0 and validated by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays. The mice xenograft model was established to investigate the roles of <i>NEAT1 in vivo</i>. <b><i>Results:</i></b> <i>NEAT1</i> was highly expressed and miR-138-5p was lowly expressed in BC tissues and cells. <i>NEAT1</i> interference or miR-138-5p restoration repressed cell proliferation, migration, and invasion but accelerated apoptosis in BC cells. Moreover, miR-138-5p directly interacted with <i>NEAT1</i> and its knockdown reversed the suppressive impact of <i>NEAT1</i> downregulation on the progression of BC cells. In addition, <i>ZFX</i> was a downstream target of miR-138-5p and its upregulation attenuated the antitumor role of miR-138-5p in BC cells. Besides, <i>ZFX</i> expression was positively regulated by <i>NEAT1</i> and inversely modulated by miR-138-5p. Furthermore, interference of <i>NEAT1</i> inhibited tumor growth by upregulating miR-138-5p and downregulating <i>ZFX</i>. <b><i>Conclusion:</i></b> <i>NEAT1</i> affected BC progression through modulating miR-138-5p/<i>ZFX</i> axis, providing a vital theoretical basis for BC treatment.