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miR-27a 通过靶向 KRAS 在食管鳞癌中发挥抑癌作用。

microRNA-27a functions as a tumor suppressor in esophageal squamous cell carcinoma by targeting KRAS.

机构信息

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.

出版信息

Oncol Rep. 2014 Jan;31(1):280-6. doi: 10.3892/or.2013.2807. Epub 2013 Oct 23.

Abstract

microRNAs (miRNAs) have been suggested to play a vital role in regulating tumor progression and invasion. However, the expression of miR-27a in esophageal squamous cell carcinoma (ESCC) and its effect on the tumorigenesis of ESCC are unclear. In the present study, we found that miR-27a was downregulated in esophageal carcinoma cell lines and ESCC specimens with lymph node metastasis. Furthermore, we demonstrated that miR-27a binds to the 3'-untranslated region (UTR) of KRAS and inhibits the expression of the KRAS protein. miR-27a levels were inversely correlated with levels of KRAS mRNA and protein in ESCC specimens. Both in vitro and in vivo assays revealed that miR-27a attenuated ESCC proliferation, invasion and tumor growth in nude mice. miR-27a exerts its tumor suppressor function through inhibition of the KRAS-related ERK pathways. Our findings suggest, for the first time, that miR-27a suppresses tumorigenesis of ESCC by targeting KRAS.

摘要

微小 RNA(miRNAs)被认为在调节肿瘤进展和侵袭方面发挥着重要作用。然而,miR-27a 在食管鳞状细胞癌(ESCC)中的表达及其对 ESCC 肿瘤发生的影响尚不清楚。在本研究中,我们发现 miR-27a 在食管癌细胞系和伴有淋巴结转移的 ESCC 标本中表达下调。此外,我们证明 miR-27a 与 KRAS 的 3'-非翻译区(UTR)结合并抑制 KRAS 蛋白的表达。ESCC 标本中 miR-27a 的水平与 KRAS mRNA 和蛋白的水平呈负相关。体外和体内实验均表明,miR-27a 可减弱 ESCC 在裸鼠中的增殖、侵袭和肿瘤生长。miR-27a 通过抑制 KRAS 相关的 ERK 通路发挥其肿瘤抑制功能。我们的研究结果首次表明,miR-27a 通过靶向 KRAS 抑制 ESCC 的肿瘤发生。

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