Cancer Gene Therapy (2018) 25:58–67
Long non-coding RNA DLEU1 predicts poor prognosis of gastric
cancer and contributes to cell proliferation by epigenetically
Received: 16 August 2017 / Revised: 23 September 2017 / Accepted: 14 October 2017 / Published online: 27 December 2017
© Nature America, Inc., part of Springer Nature 2018
Currently, accumulating documents have paid great attention to the critical role of long non-coding RNAs. The long non-
coding RNAs DLEU1 has been demonstrated to be dysregulated in many solid tumors and hematological malignancies.
However, the detailed descriptions about its potential roles and molecular mechanism in gastric cancer (GC) are still blurry.
As for our research, it was found out that DLEU1 was observably intensiﬁed in GC tissues and cell lines. And highly
expressed DLEU1 was relevant to tumor size, advanced stage of pathology and lymph node metastasis in GC patients.
Silenced DLEU1 obviously suppressed proliferation via leading to the cell cycle arrest and inducing cell apoptosis of GC.
Furthermore, mechanistic experiments uncovered that DLEU1 could recruit LSD1 (lysine speciﬁc demethylase 1) to the
promoter regions of KLF2 and then suppressed its transcription. In addition, rescue assays revealed that the oncogenic
function mediated by DLEU1 in GC was partly by regulating KLF2. Collectively, our ﬁndings manifested that DLEU1
might serve as an oncogene in GC.
As one of the commonest malignancies, gastric cancer (GC)
has always been a severe handicap for public health around
the world [1, 2]. Owing to lacking effective methods for early
diagnosis and comprehensive and effective methods for late-
stage treatment, the clinical outcomes for patients suffering
from GC were generally dismal [3–5]. Because of the fact that
GC belongs to the complicated gene-related diseases, a fur-
ther investigation about the underlying molecular mechan-
isms is essential for developing novel treatments for GC.
It has been reported that only < 2% of the mammalian
genome is able to code protein, whereas > 98% of the human
genome transcripts is non-coding RNAs (ncRNAs) without
protein-coding ability [6–8]. Long non-coding RNAs
(lncRNAs), longer than 200nt, have been identiﬁed to be
exceptionally expressed in diverse human diseases, including
tumorgenesis [9–12]. For instance, HOTAIR, a well-known
lncRNA, has been proved to be abnormally expressed in a
variety of cancers like esophageal squamous cell carcinoma
, pancreatic cancer , and renal cell carcinoma .
And still many lncRNAs have been proved to be associated
with the initiation and progression of GC. As illustrated in
the following: MALAT1 improves the metastasis and
tumorigenesis of GC by regulating vasculogenic mimicry
and angiogenesis ; SNHG5 modulates cell proliferation
and migration of GC by targeting KLF4 ; and HOXA11-
AS motivates cell proliferation and invasion in GC by scaf-
folding the chromatin modiﬁcation factors PRC2, LSD1, and
DNMT1 . Despite various lncRNAs have been identiﬁed,
the detailed bio-function and molecular mechanisms of
lncRNAs in GC still need to be further clariﬁed.
LncRNA DLEU1 (CR450325.1), located on chromo-
some 13q14.3, has been reported to be dysregulated in
chronic lymphocytic leukemia, multiple myeloma, atypical
spindle cell lipoma, and breast cancer [19–22]. Never-
theless, the biological effects and potential molecular
mechanisms of DLEU1 in the tumorigenesis of GC are still
uncertain. In our study, we ﬁgured out that DLEU1 was
obviously strengthened in GC tissues and cell lines, and
Xiaobin Li and Zongze Li contributed equally to this manuscript.
* Yimin Song
Department of General Surgery, Peking Union Medical College
Hospital, Chinese Academy of Medical Sciences&Peking Union
Medical College, Beijing 100730, P. R. China