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.

大量研究表明，microRNA（miRNA）高度参与胰腺癌的发展。但是，许多miRNA的功能作用在胰腺癌中仍然难以捉摸。在本研究中，我们分析了以前发表的微阵列数据，发现miR-1469-5p是胰腺肿瘤中最上调的miRNA之一。我们的进一步研究表明，miR-1469-5p在收集的胰腺肿瘤中高表达，其上调与淋巴结转移和晚期TNM期肿瘤相关。使用miR-1469-5p抑制剂的功能分析表明，miR-1469-5p的下调抑制了胰腺癌细胞的增殖和侵袭。机械上，miR-1469-5p与转移抑制因子NDRG1 mRNA直接相互作用，并下调NDRG1的表达以激活胰腺癌细胞中的NF-κB通路。还发现miR-1469-5p降低了E-钙黏着蛋白是一种在胰腺癌细胞中被NF-κB通路抑制的转移相关基因。NDRG1小干扰RNA（siRNA）的转染减弱了胰腺癌细胞中miR-1469-5p抑制剂的功能。此外，miR-1469-5p表达与胰腺肿瘤中的NDRG1和E-钙粘蛋白mRNA水平呈负相关。两者合计，miR-1469-5p可能通过调节NDRG1 /NF-κB/ E-钙黏着蛋白轴来发挥其在胰腺癌中的潜在潜能，表明其作为胰腺癌的预后生物标志物可能具有临床价值。