Gastric cancer is the third leading cause of cancer-related mortality worldwide. Recently, it has been demonstrated that gastric cancer cells display a specific miRNA expression profile, with increasing evidence of the role of miRNA-9 in this disease. miRNA-9 upregulation has been shown to influence the expression of E-cadherin-encoding gene, triggering cell motility and invasiveness. In this study, we designed LNA anti-miRNA oligonucleotides with a complementary sequence to miRNA-9 and tested their properties to both detect and silence the target miRNA. We could identify and visualize the in vitro uptake of low-dosing LNA-based anti-miRNA oligonucleotides without any carrier or transfection agent, as early as 2 h after the addition of the oligonucleotide sequence to the culture medium. Furthermore, we were able to assess the silencing potential of miRNA-9, using different LNA anti-miRNA oligonucleotide designs, and to observe its subsequent effect on E-cadherin expression. The administration of anti-miRNA sequences even at low-doses, rapidly repressed the target miRNA, and influenced the expression of E-cadherin by significantly increasing its levels.

中文翻译：

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使用锁定的核酸寡核苷酸靶向胃癌细胞中的miR-9。

胃癌是全球癌症相关死亡率的第三大主要原因。最近，已经证明胃癌细胞显示出特定的miRNA表达谱，并且越来越多的证据表明miRNA-9在该疾病中的作用。已显示miRNA-9上调会影响E-钙粘蛋白编码基因的表达，从而触发细胞运动性和侵袭性。在这项研究中，我们设计了具有与miRNA-9互补序列的LNA抗miRNA寡核苷酸，并测试了它们的特性以检测和沉默目标miRNA。我们可以在将寡核苷酸序列添加到培养基中后的2小时内，识别并可视化低剂量，不含任何载体或转染剂的低剂量基于LNA的抗miRNA寡核苷酸的体外吸收。此外，我们能够使用不同的LNA抗miRNA寡核苷酸设计评估miRNA-9的沉默潜力，并观察其随后对E-钙粘蛋白表达的影响。甚至在低剂量时也可以施用抗miRNA序列，迅速抑制靶标miRNA，并通过显着提高其水平来影响E-cadherin的表达。