LncRNA‐DANCR contributes to lung adenocarcinoma progression by sponging miR‐496 to modulate mTOR expression

Abstract

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 volumes in vivo compared with those of the control group. In conclusion, this study showed that DANCR might be an oncogenic lncRNA that regulates mTOR expression through directly binding to miR‐496. DANCR may be regarded as a biomarker or therapeutic target for ADC.

Long noncoding RNA DANCR confers cytarabine resistance in acute myeloid leukemia by activating autophagy via the miR‐874‐3P/ATG16L1 axis

“…One critical mechanism by which lncRNAs regulate gene expression is acting as ceRNAs to sponge targeted miRNAs (Salmena et al, 2011). This is also true for DANCR, not only because several miRNAs have been identified as direct targets of DANCR, but also the function of DANCR is prominently mediated through downregulating the expression of these miRNAs, as reported by recent studies Lu et al, 2018;Wang et al, 2018a;Wang et al, 2018b;Xu et al, 2018;Yang et al, 2018), to name a few. Combining predictive methods and some biochemical experiments, we demonstrate that miR-874-3P is a new binding target of DANCR and that by suppressing the inhibitory effect of miR-874-3P on ATG16L1 expression via interacting and decreasing miR-874-3P level, DANCR possesses an ability to upregulate ATG16L1 expression.…”

Angelica Sinensis Polysaccharide Suppresses Epithelial-Mesenchymal Transition and Pulmonary Fibrosis via a DANCR/AUF-1/FOXO3 Regulatory Axis

“…Both assays revealed that DANCR was primarily located in the cytoplasm (Fig. 4A and B), which suggested that DANCR can regulate downstream signaling at the posttranscriptional level [21,31]. To investigate the underlying mechanism by which DANCR regulates FOXO3, we analyzed the secondary structure of DANCR.…”

“…The lncRNA DANCR (differentiation antagonizing non-protein coding RNA) is a newly identified lncRNA with pivotal roles in cell proliferation, migration, invasion, and stem cell differentiation [20][21][22]. DANCR was first described as a lncRNA that blocks the differentiation of the epidermal progenitor cells [23,24].…”

Exosome-transmitted lncRNA UFC1 promotes non-small-cell lung cancer progression by EZH2-mediated epigenetic silencing of PTEN expression

“…Fox example, LINC00968 acts as an oncogene in NSCLC by activating Wnt signaling pathway 10 . DANCR acts as a ceRNA for miR-496 to regulate the expression of mTOR, thus promoting NSCLC growth 11 . LINC00473 is highly induced by LKB1 inactivation and LINC00473 upregulation promotes the growth of LKB1-inactivated NSCLC cells 12 .…”