DANCR contributed to hepatocellular carcinoma malignancy via sponging miR‐216a‐5p and modulating KLF12

Abstract

Long noncoding RNA (lncRNA) differentiation antagonizing nonprotein coding RNA (DANCR) has been identified as an oncogene in several cancers. However, the biological function and role of DANCR in hepatocellular carcinoma (HCC) remain unclear. Our current study aimed to investigate the detailed mechanism of DANCR in HCC. We found that DANCR was significantly upregulated in HCC cell lines in comparison to LO2 cells. Then, we observed that knockdown of DANCR could greatly inhibit Huh7 and HepG2 cell proliferation. In addition, HCC cell apoptosis was increased by silence of DANCR and meanwhile, cell cycle progression was blocked in G1 phase. Apart from these, downregulation of DANCR repressed HCC cell migration and invasion ability obviously. As predicted by the bioinformatics analysis, microRNA‐216a‐5p (miR‐216a‐5p) could serve as a direct target of DANCR. MiR‐216a‐5p has been reported to be involved in many cancers. Here, the correlation between miR‐216a‐5p and DANCR was confirmed using dual‐luciferase reporter assay and radioimmunoprecipitation assay. Subsequently, Kruppel‐like factor 12 (KLF12) exerts an important role in different tumor types. KLF12 can function as a downstream target of miR‐216a‐5p. Finally, the in vivo experiments were used and the data proved that DANCR also strongly suppressed HCC tumor growth in vivo via targeting miR‐216a‐5p and KLF12. In conclusion, our study indicated that DANCR might provide a new perspective for HCC treatment.

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.…”

Long non-coding RNA DANCR alleviates hypoxia-caused H9c2 cells damage through up regulation of HIF-1α

“…LncRNA discrimination antagonising non-protein coding RNA (DANCR) encodes human chromosome 4q12 and it was firstly identified as epidermal cell differentiation suppressor [12], but further study revealed that it acted as an oncogene in various kinds of cancers, such as colon cancer [13], prostate cancer [14] and hepatocellular carcinoma [15]. However, the effect of DANCR in cardiovascular diseases has never been explored.…”

<p>Meta-analysis of the prognostic value of <em>lncRNA DANCR</em> for cancer patients in China</p>

“…27 Additionally, Wang et al found that DANCR could strongly suppress HCC proliferation via targeting miR-216a-5p and KLF12. 42 43 These results reveal that lncRNA DANCR may be a crucial prognostic factor for cancer patients. Nevertheless, the underlying mechanisms by which lncRNA DANCR affects cancer remain unknown so far.…”