Targeting miR-9 in gastric cancer cells using locked nucleic acid oligonucleotides

IF 2.946 Q3 Biochemistry, Genetics and Molecular Biology BMC Molecular Biology Pub Date : 2018-06-07 DOI:10.1186/s12867-018-0107-6
Joana Filipa Lima, Joana Carvalho, Inês Pinto-Ribeiro, Carina Almeida, Jesper Wengel, Laura Cerqueira, Céu Figueiredo, Carla Oliveira, Nuno Filipe Azevedo
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引用次数: 15

Abstract

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.

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利用锁定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的第三大原因。最近,研究表明胃癌细胞显示出特定的miRNA表达谱,越来越多的证据表明miRNA-9在该疾病中的作用。miRNA-9上调已被证明会影响e -钙粘蛋白编码基因的表达,引发细胞运动和侵袭性。在这项研究中,我们设计了与miRNA-9序列互补的LNA抗miRNA寡核苷酸,并测试了它们检测和沉默靶miRNA的性能。我们可以识别和可视化低剂量的na基抗mirna寡核苷酸的体外摄取,无需任何载体或转染剂,早在2?H后加入寡核苷酸序列到培养基中。此外,我们能够评估miRNA-9的沉默潜力,使用不同的LNA抗mirna寡核苷酸设计,并观察其对E-cadherin表达的后续影响。即使是低剂量的抗miRNA序列,也能迅速抑制目标miRNA,并通过显著提高E-cadherin的水平来影响其表达。
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来源期刊
BMC Molecular Biology
BMC Molecular Biology 生物-生化与分子生物学
CiteScore
4.80
自引率
0.00%
发文量
0
审稿时长
>12 weeks
期刊介绍: BMC Molecular Biology is an open access journal publishing original peer-reviewed research articles in all aspects of DNA and RNA in a cellular context, encompassing investigations of chromatin, replication, recombination, mutation, repair, transcription, translation and RNA processing and function.
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