Silencing of lncRNA NEAT1 inhibits esophageal squamous cell carcinoma proliferation, migration, and invasion via regulation of the miR-1299/MMP2 axis

Abstract

AbstractEsophageal squamous cell carcinoma (ESCC) is the most prevalent form of esophageal cancer worldwide. Considerable evidence has verified that abnormal expression of lncRNAs can effectively influence the progression of various malignant tumors. However, the regulatory mechanisms of lncRNAs underlying ESCC development and progression remain poorly defined. Here, we investigated the role of lncRNA nuclear-enriched abundant transcript 1 (NEAT1) in ESCC via regulating microRNA 1299 (miR-1299) and matrix metalloproteinase 2 (MMP2). A total of 32 ESCC tissue samples were obtained from the First Affiliated Hospital of Zhengzhou University. The mRNA levels of lncRNA NEAT1, miR-1299, and MMP2 mRNA were measured via quantitative real-time PCR. Interactions among miR-1299, lncRNA NEAT1, and MMP2 mRNA in EC9706 cells were confirmed by dual-luciferase reporter assays and RNA immunoprecipitation (RIP) assays. The proliferation and migration/invasion of ESCC cells were verified by CCK-8 and transwell assays, respectively. lncRNA NEAT1 was up-regulated in ESCC tissues and cells. lncRNA NEAT1 silencing inhibited migration, invasion, and proliferation of ESCC cells. Furthermore, lncRNA NEAT1 sponged and negatively regulated miR-1299, thus giving rise to increased expression of MMP2. Moreover, miR-1299 inhibitors and MMP2 rescued the invasion of ESCC cells following silencing of lncRNA NEAT1. lncRNA NEAT1 was overexpressed in ESCC tissues and cells. Silencing of lncRNA NEAT1 inhibited ESCC proliferation, migration, and invasion via reducing competitive binding of lncRNA NEAT1 with miR-1299 and enhancing miR-1299-targeted suppression of MMP2. Taken together, our findings suggest that lncRNA NEAT1 is a potential target for ESCC therapy and rehabilitation.