The novel miR-9500 regulates the proliferation and migration of human lung cancer cells by targeting Akt1

被引:30
作者
Yoo, J. K. [1 ]
Jung, H. Y. [1 ]
Lee, J. M. [1 ]
Yi, H. [1 ]
Oh, S-H [2 ]
Ko, H. Y. [3 ]
Yoo, H. [1 ]
Kim, H-R [3 ]
Song, H. [3 ]
Kim, S. [3 ]
Kim, J. K. [1 ]
机构
[1] CHA Univ, Coll Pharm, Dept Pharm, Songnam 463836, Gyeonggi Do, South Korea
[2] CHA Univ, CHA Bundang Med Ctr, Dept Neurol, Songnam 463836, Gyeonggi Do, South Korea
[3] CHA Univ, Coll Life Sci, Dept Biomed Sci, Seoul 135907, South Korea
基金
新加坡国家研究基金会;
关键词
CYCLE ARREST; MICRORNAS; GENES; SURVIVAL; PATHWAY; GROWTH; TRANSCRIPTION; EXPRESSION; CLUSTER; RNAS;
D O I
10.1038/cdd.2014.33
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
MicroRNAs have crucial roles in lung cancer cell development. They regulate cell growth, proliferation and migration by mediating the expression of tumor suppressor genes and oncogenes. We identified and characterized the novel miR-9500 in human lung cancer cells. The miR-9500 forms a stem-loop structure and is conserved in other mammals. The expression levels of miR-9500 were reduced in lung cancer cells and lung cancer tissues compared with normal tissues, as verified by TaqMan miRNA assays. It was confirmed that the putative target gene, Akt1, was directly suppressed by miR-9500, as demonstrated by a luciferase reporter assay. The miR-9500 significantly repressed the protein expression levels of Akt1, as demonstrated via western blot, but did not affect the corresponding mRNA levels. Akt1 has an important role in lung carcinogenesis, and depletion of Akt1 has been shown to have antiproliferative and anti-migratory effects in previous studies. In the current study, the overexpression of miR-9500 inhibited cell proliferation and the expression of cell cycle-related proteins. Likewise, the overexpression of miR-9500 impeded cell migration in human lung cancer cells. In an in vivo assay, miR-9500 significantly suppressed Fluc expression compared with NC and ASO-miR-9500, suggesting that cell proliferation was inhibited in nude mice. Likewise, miR-9500 repressed tumorigenesis and metastasis by targeting Akt1. These data indicate that miR-9500 might be applicable for lung cancer therapy.
引用
收藏
页码:1150 / 1159
页数:10
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