Open AccessSilencing of DLEU 2 suppresses pancreatic cancer cell proliferation and invasion by upregulating microRNA‐455
Author(s) -
Xu Baoli,
Gong Xufei,
Zi Li,
Li Guang,
Dong Shuxiao,
Chen Xinrui,
Li Yutao
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13987
Subject(s) - gene knockdown , smad , microrna , gene silencing , cell growth , downregulation and upregulation , cancer research , pancreatic cancer , biology , competing endogenous rna , rna interference , cell , cell culture , chemistry , microbiology and biotechnology , cancer , rna , long non coding rna , signal transduction , gene , biochemistry , genetics
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 .