Long non-coding RNA DLGAP1-AS1 facilitates tumorigenesis and epithelial–mesenchymal transition in hepatocellular carcinoma via the feedback loop of miR-26a/b-5p/IL-6/JAK2/STAT3 and Wnt/β-catenin pathway

Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies worldwide, and epithelial–mesenchymal transition (EMT) is a crucial factor affecting HCC progression and metastasis. Long noncoding RNAs (lncRNAs) have been validated to act as critical regulators of biological processes in various tumors. Herein, we attempted to elucidate the uncharacterized function and mechanism of lncRNA DLGAP1-AS1 in regulating tumorigenesis and EMT of HCC. In our study, DLGAP1-AS1 was shown to be upregulated in HCC cell lines and capable to promote HCC progression and EMT. Besides, DLGAP1-AS1 was proven to serve as a molecular sponge to sequester the HCC-inhibitory miRNAs, miR-26a-5p and miR-26b-5p, thus enhancing the level of an oncogenic cytokine IL-6, which could activate JAK2/STAT3 signaling pathway and reciprocally elevate the transcriptional activity of DLGAP1-AS1, thus forming a positive feedback loop. Moreover, we elaborated that the cancerogenic effects of DLGAP1-AS1 in HCC cells could be effectuated via activating Wnt/β-catenin pathway by positively regulating CDK8 and LRP6, downstream genes of miR-26a/b-5p. In conclusion, our results demonstrated the detailed molecular mechanism of DLGAP1-AS1 in facilitating HCC progression and EMT in vitro and in vivo, and suggested the potentiality of DLGAP1-AS1 as a therapeutic target for HCC.