STAT3-induced upregulation of lncRNA CASC11 promotes the cell migration, invasion and epithelial-mesenchymal transition in hepatocellular carcinoma by epigenetically silencing PTEN and activating PI3K/AKT signaling pathway

Accumulating evidence suggest that long noncoding RNAs (lncRNAs) are dysregulated in various tumors and serve as crucial regulators in biological processes. Based on The Cancer Genome Atlas (TCGA) database, upregulation of CASC11 was associated with the low overall survival rate of patients with Hepatocellular carcinoma (HCC). However, the function and mechanism of lncRNA CASC11 in the progression of HCC remain unclear. Therefore, we further analyzed the expression pattern and biological role of CASC11 in HCC. CASC11 was found to be overexpressed in HCC tissues and cell lines and predicted a poor prognosis. Loss of CASC11 function efficiently suppressed cell migration, invasion and epithelial-mesenchymal transition (EMT). The mechanism which led to the upregulation of CASC11 was investigated. CASC11 was found to be activated by the transcription factor STAT3. Mechanically, the enhancer of zeste homolog 2 (EZH2) was found to be a binding partner of CASC11. Moreover, CASC11 epigenetically silenced PTEN by binding with EZH2. Finally, rescue assays were conducted to make confirmation. The present results revealed that CASC11 may be potential therapeutic target in HCC. •LncRNA CASC11 played oncogenic role in HCC.•CASC11 was activated by the transcription activator STAT3.•CASC11 epigenetically silenced PTEN by interacting with EZH2.•LncRNA CASC11 activated PI3K/AKT signaling pathway.