LncRNA-DANCR contributes to lung adenocarcinoma
progression by sponging miR-496 to modulate mTOR
, Zhuang-hua Rui
, Zhong-liang Guo
, Wang Xie
, Shan Shan
, Tao Ren
Department of Respiratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
Department of Respiratory Medicine, Shanghai Jiao Tong University Afﬁliated Sixth People’s Hospital, China
Received: May 18, 2017; Accepted: September 20, 2017
Long non-coding RNAs (lncRNAs) have emerged as new and important regulators of pathological processes including tumour development. In
this study, we demonstrated that differentiation antagonizing non-protein coding RNA (DANCR) was up-regulated in lung adenocarcinoma
(ADC) and that the knockdown of DANCR inhibited tumour cell proliferation, migration and invasion and restored cell apoptosis rescued;
cotransfection with a miR-496 inhibitor reversed these effects. Luciferase reporter assays showed that miR-496 directly modulated DANCR;
additionally, we used RNA-binding protein immunoprecipitation (RIP) and RNA pull-down assays to further conﬁrm that the suppression of
DANCR by miR-496 was RISC-dependent. Our study also indicated that mTOR was a target of miR-496 and that DANCR could modulate the
expression levels of mTOR by working as a competing endogenous RNA (ceRNA). Furthermore, the knockdown of DANCR reduced tumour vol-
umes in vivo compared with those of the control group. In conclusion, this study showed that DANCR might be an oncogenic lncRNA that regu-
lates mTOR expression through directly binding to miR-496. DANCR may be regarded as a biomarker or therapeutic target for ADC.
Lung cancer is the most common cancer and remains the leading
cause of cancer-related death in the world . Lung ADC is the most
common type of lung cancer, accounting for almost half of all lung
cancer cases [2, 3]. Although multimodal diagnostic methods and
treatments have been implemented in the past years, ADC is still a
lethal disease, with a 5-year survival rate of approximately 15% .
Hence, further investigation of the aetiology and biological mecha-
nisms of ADC is important for developing novel therapeutic targets
lncRNAs are a class of non-protein-coding RNAs longer than 200
nucleotides that are poorly conserved in different species . In the
past years, studies have implicated that lncRNAs functioned as regu-
lators of numerous pathological processes, such as cancer progres-
sion, metastasis and tumour drug resistance [6–8]. Several lncRNAs
have been reported to be involved in lung cancer tumorigenesis. For
example, the lncRNA MALAT-1 was reported to be extremely abun-
dant in lung cancer and was identiﬁed as a prognostic marker .
Another lncRNA, NEAT1, was identiﬁed to function as an oncogene by
acting as a ceRNA in NSCLC . However, the precise functional
roles of lncRNAs in lung cancer still need clariﬁcation.
Differentiation antagonizing non-protein coding RNA (DANCR),
also named ANCR, was reported to be widely distributed in human
organs and was ﬁrst identiﬁed as an RNA related to progenitor cell
differentiation-related RNA . In recent years, many studies have
been conducted to evaluate the function of DANCR in biological pro-
cesses, including stem cell differentiation, cell proliferation and can-
cer progression . The modulatory role of DANCR in the
progression of several types of cancer, including colorectal cancer,
hepatocellular carcinoma, prostate cancer and breast cancer, has
already been studied [13–16]. However, the role of DANCR in lung
cancer still needs to be explored and its function remains to be char-
In this study, we explored the potential involvement of DANCR in
lung ADC. We found that the expression level of DANCR is up-regu-
lated in cancer tissues compared with that in adjacent normal tissues.
When DANCR was knocked down, cancer cell proliferation, migration
and invasion were inhibited, and cell apoptosis was increased. Addi-
tionally, our study suggested that DANCR may regulate mammalian
target of rapamycin (mTOR) expression through sponging miR-496,
These authors contributed equally to this work.
*Correspondence to: Prof. Tao REN
ª 2017 The Authors.
Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use,
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J. Cell. Mol. Med. Vol 22, No 3, 2018 pp. 1527-1537