MiRNA-196 is upregulated in glioblastoma but not in anaplastic astrocytoma and has prognostic significance.
OBJECTIVE
MicroRNAs (miRNA) are short noncoding RNAs that can play critical roles in diverse biological processes. They are implicated in tumorigenesis and function both as tumor suppressors and as oncogenes. The clinical significance of miRNA expression profiles in malignant gliomas remains unclear.


METHODS
In this study, we examined the expression levels of 365 mature human miRNAs in 12 malignant gliomas, including 8 glioblastomas and 4 anaplastic astrocytomas, using TaqMan real-time quantitative PCR arrays. A validation study was done to corroborate a subset of the results, including expression levels of miR-196a, -196b, -21, and -15b, by analyzing 92 malignant gliomas by conventional real-time PCR. We modeled the relationship between the expression levels of these miRNAs and the survival rate of 39 glioblastoma patients by Kaplan-Meier method and multivariate analysis.


RESULTS
Expression profiles in glioblastomas and anaplastic astrocytomas suggested that 16 miRNAs were candidate markers associated with the malignant progression of gliomas. Among them, miR-196a showed the most significant difference (P = 0.0038), with miR-196b also having a high significance (P = 0.0371). Both miRNAs showed increased expression levels in glioblastomas relative to both anaplastic astrocytomas and normal brains in the validation study. Furthermore, patients with high miR-196 expression levels showed significantly poorer survival by the Kaplan-Meier method (P = 0.0073). Multivariate analysis showed that miR-196 expression levels were an independent predictor of overall survival in all 39 glioblastoma patients (P = 0.021; hazard ratio, 2.81).


CONCLUSIONS
Our results suggest that miR-196 may play a role in the malignant progression of gliomas and may be a prognostic predictor in glioblastomas.
Guan
Yanlei
Y
Department of Neurosurgery and Neuropathology, Kyushu University, Fukuoka, Japan.
Mizoguchi
Masahiro
M
Yoshimoto
Koji
K
Hata
Nobuhiro
N
Shono
Tadahisa
T
Suzuki
Satoshi O
SO
Araki
Yukie
Y
Kuga
Daisuke
D
Nakamizo
Akira
A
Amano
Toshiyuki
T
Ma
Xinlong
X
Hayashi
Kenshi
K
Sasaki
Tomio
T
D001254:Astrocytoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015870:Gene Expression; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D019656:Loss of Heterozygosity; D035683:MicroRNAs / Q000235:genetics*; D018895:Microsatellite Repeats; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C542543:MIRN196 microRNA, human; D035683:MicroRNAs