MiRNA-196 Is Upregulated in Glioblastoma But Not in Anaplastic Astrocytoma and Has Prognostic Significance

Abstract

Purpose: 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.Experimental Design: 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 realtime 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. Clin Cancer Res; 16(16); 4289-97. ©2010 AACR.

The Role of microRNAs in Gliomas and Their Potential Applications for Diagnosis and Treatment

“…Other papers have demonstrated that miRNAs can be used for tumor classification and grading 66,67 in addition to the diagnosis 23 , prognosis 22,23 and prediction of therapeutic efficacy 69,69 of tumors. The discovery of miRNAs in the serum of cancer patients 70 opened up the exciting possibility of using miRNAs as non-invasive biomarkers.…”

“…Multivariate analysis showed that the expression of both these miRNAs is a predictor of overall survival in glioblastoma patients 22,23 . Analysis of miRNA expression data in glioblastoma patients (n = 222) derived from the TCGA dataset identified an expression signature of ten miRNAs that can predict glioblastoma (GBM) patient survival 71 .…”

“…Detecting and quantifying microRNAs in tissue and serum will soon be routinely used for tumor classification and grading as well as diagnostic and prognostic testing for gliomas. For example, high levels of miR-21, miR-182 and miR-196 as well as low expression of miR-181b and miR-106a are associated with poor overall survival in patients with malignant gliomas [22][23][24] , and these miRNAs might function as biomarkers of glioma progression. Furthermore, miR-195, miR-455-3p, miR-10a 25 and the miR-181 family 26 have been linked to treatment resistance, and assessing the relative expression levels of these miRNAs may assist with the design of personalized treatments.…”

MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics

“…The signature included three miRNAs (miR‐20a, miR‐106a, and miR‐17‐5p) that were protective and seven (miR‐31, miR‐222, miR‐148a, miR‐221, miR‐146b, miR‐200b, and miR‐193a) that were risky with respect to the association between their expression and patient survival. Additionally, other studies have found that high expression of miR‐21, miR‐182, and miR‐196 as well as low expression of miR‐181b and miR‐106a are associated with poor patient outcomes 19, 85, 86.…”

Estudo funcional de microRNAs associados ao carcinoma epidermóide em cultura de células orais

“…TaqMan miRNA Reverse Transcription kit (Life Technologies™) utilizando-se primers específicos para os miRNAs miRNA-1, miRNA-7, miRNA-10b, miRNA-196a e para o gene de referência RNU48, pequenos RNAs nucleares (Guan et al, 2010 histograma e o conteúdo de DNA distribui as células em "G1+G0", "S" e "G2+M". A discriminação entre as diferentes fases do ciclo é feita pela intensidade de fluorescência, sendo que a fase "G2+M" sempre apresenta o dobro de fluorescência que a fase "G1+G0", pois o DNA nesta fase encontra-se duplicado, enquanto a distância entre "G1+G0" e "G2+M", apresenta uma quantidade intermediária de DNA sendo caracterizada como a fase de síntese, "S".…”