期刊
NEUROSCIENCE LETTERS
卷 546, 期 -, 页码 36-41出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2013.04.030
关键词
Anaplastic astrocytoma; Glioblastoma multiforme; Ki-67; miRNA; mRNA
资金
- National Natural Science Foundation of China [81201993]
- International S&T Cooperation Program of China [2012DFA30470]
- National High Technology Research and Development Program of China (863) [2012AA02A508]
Background: Ki-67 is an excellent indicator of glioma cell growth. However, limited information is available regarding the mechanisms underlying abnormal expression of Ki-67 in glioma tissue. The aim of this study is to identify Ki-67 specific miRNA-mRNA interactions on basis of miRNA and mRNA expression profilings. Methods: We performed a large-scale miRNA (n = 829) and mRNA (n = 29,421) expression profiling in primary glioblastoma multiforme (pGBM) and anaplastic astrocytoma (AA) tissues (with an aim to investigate Ki-67 related miRNAs and mRNAs). From target prediction databases, the targeting relationships between Ki-67 specific miRNAs and mRNAs were established, and functions of these mRNAs were analyzed by DAVID. The functional verifications of the candidate miRNA were also performed in LN229 cell line. Results: High expression level of Ki-67 protein predicted a shorter survival time for patients with AA. Integrated analysis of profiling data from pGBM and AA revealed 4 Ki-67 positively and 5 negatively correlated miRNAs, along with the top 12 Ki-67 positively and 2 negatively correlated mRNAs. By means of target prediction, we found that the target mRNAs employed by miR-218 were the most significant among Ki-67 specific mRNAs. Up-regulation of miR-218 was further demonstrated to reduce Ki-67 expression, promote apoptosis, and induce G0/G1 phase cell cycle arrest in LN229 cells. Conclusions: Ki-67 protein may be regulated by specific miRNA-mRNA interactions which may contribute to the proliferation of glioma cells. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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