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Primate-specific miR-663 functions as a tumor suppressor by targeting PIK3CD and predicts the prognosis of human glioblastoma.

Authors: Shi, Yu  Chen, Cong  Zhang, Xia  Liu, Qing  Xu, Jin-Ling  Zhang, Hua-Rong  Yao, Xiao-Hong  Jiang, Tao  He, Zhi-Cheng  Ren, Yong  Cui, Wei  Xu, Chuan  Liu, Ling  Cui, You-Hong  Yu, Shi-Zhu  Ping, Yi-Fang  Bian, Xiu-Wu 
Citation: Shi Y, etal., Clin Cancer Res. 2014 Apr 1;20(7):1803-13. doi: 10.1158/1078-0432.CCR-13-2284. Epub 2014 Feb 12.
Pubmed: (View Article at PubMed) PMID:24523440
DOI: Full-text: DOI:10.1158/1078-0432.CCR-13-2284


PURPOSE: To determine the prognostic significance of miR-663 in glioblastoma, its effect in tumor progression, and the underlying mechanism.
EXPERIMENTAL DESIGN: Specimens from 256 cases of patients with glioma, including 239 patients with follow-up information, were used to analyze the association between miR-663 and patients' prognosis by Kaplan-Meier and multivariate Cox regression analyses. The effects of miR-663 on glioblastoma cell proliferation and invasion were examined both in vitro and in vivo. Bioinformatics prediction and signal network analysis were applied to identify the putative targets of miR-663, which were further verified by luciferase reporter assay, rescue experiments as well as the immunohistochemistry (IHC) and Western blotting examination of downstream effectors. Quantitative reverse transcriptase PCR (qRT-PCR) and IHC were applied to investigate the clinical association between miR-663 and its target in human glioblastoma specimens.
RESULTS: miR-663 was inversely correlated with glioma grades but positively correlated with patients' survival. Furthermore, two distinct subgroups of patients with glioblastoma with different prognoses were identified on the basis of miR-663 expression in our specimens and that from The Cancer Genome Atlas (TCGA) database. Overexpression of miR-663 significantly suppressed the proliferation and invasion of glioblastoma cells in vitro and in vivo. Mechanistically, we discovered PIK3CD as a direct target of miR-663 and found that phosphorylated AKT and three key downstream effectors of PIK3CD, i.e., CCND1, MMP2, and MMP7, were downregulated by miR-663 overexpression. Moreover, PIK3CD was inversely correlated with miR-663 in glioblastoma specimens and predicted poor prognosis of patients with glioblastoma.
CONCLUSION: miR-663 is a novel prognostic biomarker and a potential therapeutic candidate for glioblastoma.

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CRRD Object Information
CRRD ID: 13782051
Created: 2018-08-16
Species: All species
Last Modified: 2018-08-16
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.