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Molecular and Cellular Biochemistry

, Volume 403, Issue 1–2, pp 33–41 | Cite as

MiR-1224-5p acts as a tumor suppressor by targeting CREB1 in malignant gliomas

  • Jin Qian
  • Rui Li
  • Ying-Yi Wang
  • Yan Shi
  • Wen-Kang Luan
  • Tao Tao
  • Jun-Xia Zhang
  • Yi-Chang Xu
  • Yong-Ping You
Article

Abstract

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 low-grade 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.

Keywords

MiR-1224-5p CREB1 Glioma Cell proliferation Invasion Apoptosis 

Notes

Acknowledgments

This work was supported by grants from the National High Technology Research and Development Program of China (863) (2012AA02A508), the 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), and Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU, and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Supplementary material

11010_2015_2334_MOESM1_ESM.docx (10 kb)
Supplementary material 1 (DOCX 10 kb)
11010_2015_2334_MOESM2_ESM.tif (73 kb)
Supplementary material 2 (TIFF 73 kb)

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Jin Qian
    • 1
    • 2
  • Rui Li
    • 1
  • Ying-Yi Wang
    • 1
  • Yan Shi
    • 1
    • 3
  • Wen-Kang Luan
    • 1
  • Tao Tao
    • 1
  • Jun-Xia Zhang
    • 1
  • Yi-Chang Xu
    • 2
  • Yong-Ping You
    • 1
  1. 1.Department of NeurosurgeryThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.Department of NeurosurgeryThe People’s Hospital of Xuancheng CityXuanchengChina
  3. 3.Department of Neurosurgery, Nanjing First HospitalNanjing Medical UniversityNanjingChina

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