MicroRNA-1469-5p promotes the invasion and proliferation of pancreatic cancer cells via direct regulating the NDRG1/NF-κB/E-cadherin axis

Numerous studies demonstrated that microRNAs (miRNAs) were highly involved in pancreatic cancer development. However, the functional roles of many miRNAs remain elusive in pancreatic cancer. In the present study, we analyzed previous published microarray data and found that miR-1469-5p was one of top upregulated miRNAs in pancreatic tumors. Our further study showed that miR-1469-5p was highly expressed in collected pancreatic tumors and its upregulation was associated with lymph node metastasis and tumors of advanced TNM stage. Functional analysis with miR-1469-5p inhibitor showed that downregulation of miR-1469-5p repressed pancreatic cancer cell proliferation and invasion. Mechanistically, miR-1469-5p directly interacted with metastasis suppressor NDRG1 mRNA and downregulated expression of NDRG1 to activate NF-κB pathway in pancreatic cancer cells. It was also found that miR-1469-5p decreased expression of E-cadherin, a metastasis related gene repressed by NF-κB pathway, in pancreatic cancer cells. Transfection of NDRG1 small interference RNA (siRNA) attenuated the function of miR-1469-5p inhibitor in pancreatic cancer cells. Moreover, miR-1469-5p expression was negatively associated with NDRG1 and E-cadherin mRNA levels in pancreatic tumors. Taken together, miR-1469-5p may exert its oncogenic potential in pancreatic cancer via regulating a NDRG1/NF-κB/E-cadherin axis, suggesting that it may be clinically valuable as a prognostic biomarker of pancreatic cancer.