The positive feedback loop of lncRNA DANCR/miR-138/Sox4 facilitates malignancy in non-small cell lung cancer.

Abstract

Non-small cell lung cancer (NSCLC) is one of the most frequent cancers worldwide. The abnormal expression of long non-coding RNAs (lncRNAs) has been reported to be closely associated with the progression of human cancers, including NSCLC. Here, we demonstrated that differentiation antagonizing noncoding RNA (DANCR) was overexpressed in NSCLC tissues. Upregulation of DANCR expression was significantly associated with larger tumor size, advanced TNM stage and lymph node metastasis, and also predicted poor prognoses of patients with NSCLC. Functional experiments showed that DANCR enhanced NSCLC growth and metastasis both <i>in vitro</i> and <i>in vivo</i>. Further investigation revealed that DANCR could compete with the Sox4 mRNA to bind with miR-138, thus affecting Sox4 expression. In addition, we found that Sox4 bound to the promoter regions of <i>DANCR</i> gene to activate DANCR expression, suggesting a positive feedback loop of DANCR/miR-138/Sox4 in NSCLC. Taken together, these results provide a comprehensive analysis of the roles of DANCR as a competing endogenous RNA (ceRNA) in NSCLC progression.