期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 403, 期 1-2, 页码 33-41出版社
SPRINGER
DOI: 10.1007/s11010-015-2334-1
关键词
MiR-1224-5p; CREB1; Glioma; Cell proliferation; Invasion; Apoptosis
类别
资金
- National High Technology Research and Development Program of China (863) [2012AA02A508]
- Research Special Fund For Public Welfare Industry of Health [201402008]
- National Natural Science Foundation of China [91229121, 81272792, 81472362, 81172389, 81372709, 81302185]
- Jiangsu Province's Natural Science Foundation [20131019]
- Jiangsu Province's Key Provincial Talents Program [RC2011051]
- Jiangsu Province's Key Discipline of Medicine [XK201117]
- Jiangsu Provincial Special Program of Medical Science [BL2012028]
- Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
The dysregulation of miR-1224-5p has been reported in several human cancers. However, the expression and function of miR-1224-5p in glioma remains unknown. The aim of our study was to investigate the effect of miR-1224-5p on glioma cells and to determine its functional signaling mediators. Using 198 glioma samples within the Chinese Glioma Genome Atlas expression dataset, we demonstrated that miR-1224-5p expression is decreased in high-grade gliomas when compared with lowgrade gliomas. Differential miR-1224-5p expression in 50 randomly selected samples was verified by in situ hybridization. The expression of miR-1224-5p was shown to positively correlate with overall survival in 82 glioblastoma patients. Exogenous expression of miR-1224-5p in glioma cells suppressed proliferation and invasion and promoted apoptosis. Target prediction algorithms identified a consensus miR-1224-5p recognition site in the 3'UTR of the cAMP response element-binding protein (CREB1) gene, and this sequence was shown to directly confer miR-1224-5p repression in luciferase reporter assays. Furthermore, exogenous miR-1224-5p expression was shown to down-regulate CREB1, as well as its downstream target genes matrix metalloproteinase-9 and B-cell lymphoma-2. Conversely, over-expression of CREB1 reversed the effect of miR-1224-5p on the proliferation, invasion, and apoptosis of glioma cells. These data indicate that miR-1224-5p may inhibit tumor-associated activity in malignant gliomas by targeting CREB1.
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