Long noncoding
RNA
(lnc
RNA
)
DLEU
2
has been shown to be dysregulated in several type of tumor. However, the potential biological roles and molecular mechanisms of
DLEU
2
in pancreatic cancer (
PC
) progression are poorly understood. In this study, we found that the
DLEU
2
level was substantially upregulated in
PC
tissues and
PC
cell lines, and significantly associated with poor clinical outcomes in
PC
patients. Overexpression of
DLEU
2 significantly induced
PC
cell proliferation and invasion, whereas knockdown of
DLEU
2 impaired cell proliferation and invasion in vitro. Furthermore, bioinformatics analysis, luciferase reporter assay, and
RNA
immunoprecipitation assay revealed that
DLEU
2 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
SMAD
2 was a direct target of miR‐455, and the restoration of
SMAD
2 rescued cell growth and invasion that were reduced by
DLEU
2 knockdown or miR‐455 overexpression. In addition, low miR‐455 expression and high
SMAD
2 expression was correlated with poor patient survival. These results indicate that
DLEU
2 is an important promoter of
PC
development, and targeting the
DLEU
2/miR‐455/
SMAD
2 pathway could be a promising therapeutic approach in the treatment of
PC
.