Silencing of DLEU2 suppresses pancreatic cancer cell proliferation and invasion by upregulating microRNA‐455

摘要

Long noncoding RNA (lncRNA) DLEU2 has been shown to be dysregulated in several type of tumor. However, the potential biological roles and molecular mechanisms of DLEU2 in pancreatic cancer (PC) progression are poorly understood. In this study, we found that the DLEU2 level was substantially upregulated in PC tissues and PC cell lines, and significantly associated with poor clinical outcomes in PC patients. Overexpression of DLEU2 significantly induced PC cell proliferation and invasion, whereas knockdown of DLEU2 impaired cell proliferation and invasion in vitro. Furthermore, bioinformatics analysis, luciferase reporter assay, and RNA immunoprecipitation assay revealed that DLEU2 directly bond to microRNA‐455 (miR‐455) and functioned as an endogenous sponge for miR‐455, which could remarkably suppress cell growth and invasion. We also determined that SMAD2 was a direct target of miR‐455, and the restoration of SMAD2 rescued cell growth and invasion that were reduced by style="fixed-case">DLEU2 knockdown or miR‐455 overexpression. In addition, low miR‐455 expression and high style="fixed-case">SMAD2 expression was correlated with poor patient survival. These results indicate that style="fixed-case">DLEU2 is an important promoter of style="fixed-case">PC development, and targeting the style="fixed-case">DLEU2/miR‐455/ style="fixed-case">SMAD2 pathway could be a promising therapeutic approach in the treatment of style="fixed-case">PC.