Suppressive effect of exogenous miR-16 and miR-34a on tumorigenesis of breast cancer cells

被引:42
作者
Haghi, Mehdi [1 ,2 ]
Taha, Masoumeh F. [1 ]
Javeri, Arash [1 ]
机构
[1] Natl Inst Genet Engn & Biotechnol, Inst Med Biotechnol, Dept Stem Cells & Regenerat Med, Pajoohesh Blvd, Tehran 14965161, Iran
[2] Islamic Azad Univ, Damghan Branch, Dept Biol, Damghan, Iran
关键词
apoptosis; breast cancer; invasion; miR-16; miR-34a; TGF-BETA; DOWN-REGULATION; P38; MAPK; APOPTOSIS; EXPRESSION; CYCLE; PROLIFERATION; MICRORNA-34A; MIGRATION; INVASION;
D O I
10.1002/jcb.28608
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
Recent investigations have shown tumor-suppressive roles for miR-16 and miR-34a. They also share some features in regard to targeting cancer cell signaling pathways which they control. Therefore, in this study, we aimed to further scrutinize whether exogenous induction of mature miR-34a and miR-16 can collaborate in breast tumor suppression. MDA-MB-231 and SK-BR-3 human breast cancer cell lines were cultured and transfected twice with hsa-miR-16-5p and hsa-miR-34a-5p mimics individually or in combination. The cells were analyzed for apoptosis rate and cell cycle indices by flow cytometry. Also, the expression of several invasion and the epithelial-mesenchymal transition markers was evaluated at gene and protein levels by quantitative real-time polymerase chain reaction and western blot analysis, respectively. Assessment of invasiveness and migratory potential of the transfected cells was performed using three-dimensional spheroid formation and wound-healing assay, respectively. In both cell lines, miR-16 and miR-34a induced apoptosis and cell-cycle arrest and also suppressed invasion and migration. Some of these effects, like cell-cycle arrest and induction of apoptosis, were significantly higher when using both microRNAs than when using them individually for transfection of the cells. Our results are indicating that miR-16 and miR-34a can collaborate in breast tumor suppression.
引用
收藏
页码:13342 / 13353
页数:12
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