Purpose: Pancreatic cancer (PC) is a malignancy with poor prognosis and controversial treatment options. Long non-coding RNA (lncRNA) is a significant factor in the development of PC. In the current study, the possible effects of HOTAIR on the epithelial–mesenchymal transition (EMT) of PC and the related mechanisms were investigated.
Methods: The PC models were induced by 10 mg/100 g dimethylbenzoanthracene (DMBA) in pancreas. Mice were injected with the HOTAIR mimic and HOTAIR shRNA to determine the role of HOTAIR in PC. Subsequently, the expression of HOTAIR in PC cells was assayed. To determine the mechanism of HOTAIR in PC, human PC cell line PANC-1, Miapaca-2 and human normal pancreatic ductal epithelial cell line HPDE6-C7 were transfected with the HOTAIR mimic, the shRNA against HOTAIR, the Wnt/b-catenin activator (LiCl), and the Wnt/b-catenin inhibitor (XAV939), respectively. Moreover, the expressions of the Wnt/β-catenin signaling pathway-related genes (β-catenin, cyclinD1, c-myc, LEF-1 and c-Jun) and the levels of the EMT markers (E-cadherin, N-cadherin and Vimentin) were determined. Finally, the cell biological processes were evaluated by functional experiments.
Results: HOTAIR was found to be highly expressed in the PC cells in mice. The expression of β-catenin, cyclinD1, c-myc, LEF-1 and c-Jun, N-cadherin and Vimentin was found to be decreased, while the expression of E-cadherin was found to be increased subsequent to the silencing of HOTAIR in human PC cell lines PANC-1 and Miapaca-2. Additionally, it was observed that the silencing of HOTAIR could inhibit the Wnt/β-catenin signaling pathway to alleviate EMT of tumor cells and inhibit the capacities of cell proliferation, migration, and invasion.
Conclusion: The key finding of the present study is that the silencing of HOTAIR could potentially inhibit EMT and growth of PC through the Wnt/β-catenin signaling pathway, providing a novel therapy for PC.
Keywords: long non-coding RNA, HOTAIR, Wnt/β-catenin signaling pathway, epithelial–mesenchymal transition, pancreatic cancer