MiR-141-3p is upregulated in esophageal squamous cell carcinoma and targets pleckstrin homology domain leucine-rich repeat protein phosphatase-2, a negative regulator of the PI3K/AKT pathway
MiR-141-3p is upregulated in esophageal squamous cell carcinoma and targets pleckstrin homology domain leucine-rich repeat protein phosphatase-2, a negative regulator of the PI3K/AKT pathway
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DOI：
10.1016/j.bbrc.2018.05.025
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发表时间：
2018-06-22
影响因子：
3.1
通讯作者：
Inui, Takashi
中科院分区：
文献类型：
--
作者：
Ishibashi, Osamu;Akagi, Ichiro;Inui, Takashi
磷脂酰肌醇-3-激酶(PI3K)/AKT通路在多种人类肿瘤中经常被激活，并在肿瘤的发生发展中发挥重要作用。越来越多的证据表明，microRNAs(MiRNAs)的异常表达与肿瘤的进展和转移密切相关。本研究以食管鳞癌中调控PI3K/AKT通路相关基因的miRNAs为研究对象，利用基因芯片技术对三个人食管鳞癌细胞系和一个正常食道上皮细胞系中miRNA和mRNA的表达水平进行了综合分析，以确定食管鳞癌中上调的miRNAs及其可能的靶基因。MiRNA芯片分析显示，miR-31-5p、miR-141-3p、miR-2006-3p、miR-200C-3p和miR-205-5p在ESCC细胞系中的表达水平均高于正常食管上皮细胞系。对基因芯片数据的生物信息学分析发现，几个AKT/PI3K通路相关基因是这些miRNAs的候选靶点，其中包括肿瘤抑制基因，如DNA损伤诱导转录本4和Pleckstrin同源结构域富含亮氨酸重复蛋白磷酸酶2(PHLPP2)。为了在实验上验证相关miRNAs的靶点，将合成的miRNAs的模拟物导入食道上皮细胞系。在这里，我们报告miR-141-3p抑制AKT/P13K途径的负调控因子PHLPP2的表达，作为ESCC的靶点。(C)2018 Elsevier Inc.保留所有权利。
The phosphatidylinositol-3-kinase (PI3K)/AKT pathway is frequently activated in various human cancers and plays essential roles in their development and progression. Accumulating evidence suggests that dysregulated expression of microRNAs (miRNAs) is closely associated with cancer progression and metastasis. Here, we focused on miRNAs that could regulate genes related to the PI3K/AKT pathway in esophageal squamous cell carcinoma (ESCC).To identify upregulated miRNAs and their possible target genes in ESCC, we performed microarray-based integrative analyses of miRNA and mRNA expression levels in three human ESCC cell lines and a normal esophageal epithelial cell line. The miRNA microarray analysis revealed that miR-31-5p, miR-141-3p, miR-2006-3p, miR-200c-3p, and miR-205-5p were expressed at higher levels in the ESCC cell lines than the normal esophageal epithelial cell line. Bioinformatical analyses of mRNA microarray data identified several AKT/PI3K pathway-related genes as candidate targets of these miRNAs, which include tumor suppressors such as DNA-damage-inducible transcript 4 and pleckstrin homology domain leucine-rich repeat protein phosphatase-2 (PHLPP2). To validate the targets of relevant miRNAs experimentally, synthetic mimics of the miRNAs were transfected into the esophageal epithelial cell line. Here, we report that miR-141-3p suppress the expression of PHLPP2, a negative regulators of the AKT/P13K pathway, as a target in ESCC. (C) 2018 Elsevier Inc. All rights reserved.