MicroRNA-27a directly targets KRAS to inhibit cell proliferation in esophageal squamous cell carcinoma.
MicroRNA-27a directly targets KRAS to inhibit cell proliferation in esophageal squamous cell carcinoma.
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DOI：
10.3892/ol.2014.2701
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发表时间：
2015-01
期刊：
影响因子：
2.9
通讯作者：
Zhou H
中科院分区：
文献类型：
--
作者：
Jiang Y;Duan Y;Zhou H
MicroRNA（miRNAs）是一类通过与特定靶mRNA的3′-非翻译区结合来负调控基因表达水平的小分子非编码RNA。为探讨miR-27 a在食管鳞状细胞癌（ESCC）中的作用，应用TargetScan软件预测miR-27 a的靶基因。Kirsten大鼠肉瘤病毒癌基因同源物（KRAS）被认为是miR-27 a的潜在靶基因，是本研究的重点。当与miRNA阴性对照相比时，用miR-27 a模拟物转染的细胞中的荧光素酶活性低48%。此外，与对照相比，在用含有miR-27 a和miR-27 a结合序列的表达载体共转染的细胞中，K-ras蛋白的表达水平降低≤50%。与健康食管上皮细胞和组织相比，miR-27 a在ESCC细胞系和组织中的表达水平显著降低。然而，在miR-27 a模拟物或小干扰K-ras转染后，靶基因KRAS的表达水平上调，ESCC细胞增殖显著抑制。总之，本研究表明，miR-27 a在ESCC中的表达水平较低，并且miR-27 a直接靶向KRAS基因，导致食管癌细胞增殖抑制。
MicroRNAs (miRNAs) are a type of small non-coding RNA that negatively regulate gene expression levels by binding to the 3′-untranslated region of specific target mRNAs. To investigate the role of miR-27a in esophageal squamous cell carcinoma (ESCC), TargetScan software was used to predict the target gene of miR-27a. Kirsten rat sarcoma viral oncogene homolog (KRAS), which has been implicated as a regulator of cell proliferation, differentiation and transformation, was identified as a potential target gene of miR-27a and, thus, was the focus of the present study. Luciferase activity in cells transfected with miR-27a mimics was 48% lower when compared with that of the miRNA-negative control. Furthermore, expression levels of the K-ras protein were reduced by ≤50% in cells cotransfected with an expression vector containing miR-27a and miR-27a binding sequences, when compared with the control. The expression level of miR-27a was significantly lower in ESCC cell lines and tissues when compared with healthy esophageal epithelial cells and tissues. However, the expression level of the target gene, KRAS was upregulated and ESCC cell proliferation was significantly inhibited following miR-27a mimic or small interfering K-ras transfection. In conclusion, the present study demonstrated that the expression level of miR-27a was low in ESCC and that miR-27a directly targets the KRAS gene, resulting in inhibited cell proliferation in esophageal cancer.
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影响因子：
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作者：
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DOI：
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发表时间：
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