Integrative Analysis of Dysregulated lncRNA-Associated ceRNA Network Reveals Functional lncRNAs in Gastric Cancer

Abstract

Mounting evidence suggests that long noncoding RNAs (lncRNAs) play important roles in the regulation of gene expression by acting as competing endogenous RNA (ceRNA). However, the regulatory mechanisms of lncRNA as ceRNA in gastric cancer (GC) are not fully understood. Here, we first constructed a dysregulated lncRNA-associated ceRNA network by integrating analysis of gene expression profiles of lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs). Then, we determined three lncRNAs (<i>RP5-1120P11</i>, <i>DLEU2</i>, and <i>DDX11-AS1</i>) as hub lncRNAs, in which associated ceRNA subnetworks were involved in cell cycle-related processes and cancer-related pathways. Furthermore, we confirmed that the two lncRNAs (<i>DLEU2</i> and <i>DDX11-AS1</i>) were significantly upregulated in GC tissues, promote GC cell proliferation, and negatively regulate miRNA expression, respectively. The hub lncRNAs (<i>DLEU2</i> and <i>DDX11-AS1</i>) could have oncogenic functions, and act as potential ceRNAs to sponge miRNA. Our findings not only provide novel insights on ceRNA regulation in GC, but can also provide opportunities for the functional characterization of lncRNAs in future studies.