MicroRNA-181 family predicts response to concomitant chemoradiotherapy with temozolomide in glioblastoma patients

Abstract

MicroRNAs are endogenously expressed regulatory noncoding RNAs. Previous studies showed altered expression levels of several microRNAs in glioblastomas. In this study, we examined the expression levels of selected microRNAs in 22 primary glioblastomas and six specimens of adult brain tissue by real-time PCR method. In addition, we examined methylation status of MGMT promoter by methylation-specific real-time PCR, as this has been shown to be a predictive marker in glioblastomas. MGMT methylation status was not correlated with response to concomitant chemoradiotherapy with temozolomide (RT/TMZ). MiR-221 (p=0,016), miR-222 (p=0,038), miR-181b (p=0,036), miR-181c (p=0,043) and miR-128a (p=0,001) were significantly down-regulated in glioblastomas. The most significant change was observed for up-regulation in miR-21 expression in glioblastomas (p<0,001). MiR-181b and miR-181c were significantly down-regulated in patients who responded to RT/TMZ (p=0,016; p=0,047, respectively) in comparison to patients with progredient disease. Our data indicate for the first time that expression levels of miR-181b and miR-181c could serve as a predictive marker of response to RT/TMZ therapy in glioblastoma patients.

Analysis of circulating microRNAs in adrenocortical tumors

“…hsamiR-100 regulates the insulin-like growth factor 1 receptor/ mammalian target of rapamycin (IGF-1R/mTOR) pathway, which has an important role in the regulation of adrenocortical cell proliferation. 36 The upregulation of tissue hsa-miR181b has been previously described in ACC compared with ACA, 16,17 as well as in several cancers [38][39][40] Moreover, it was associated with poor prognosis in colon adenocarcinomas. 39 hsa-miR-181b behaves as a tumor suppressor, and can target important oncogenes such as B-cell lymphoma 2 (BCL2), 41 TIMP metallopeptidase inhibitor 3 (TIMP3) 42 and insulin-like growth factor 1 receptor (IGF1R).…”

A promising light for an impossible disease: miRNAs in malignant gliomas

“…In their study, Yu et al report plasma levels of miR-21, miR-128 and miR-342-3p being altered in GBM patients compared with normal, healthy controls [14]. In addition, the observations of Slaby et al illustrate that there is a trend of downregulation of miRNA-181b and miRNA-181c in patients with better response to concomitant radiation therapy and TMZ, in comparison to those with disease progression [15]. Overall, there is much potential for the future use of miRNAs to augment current patient monitoring.…”

MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics

“…Slaby et al. 88 also examined the correlation between expression levels of selected miRNAs and TMZ resistance in GBM, but used 22 primary GBM tumors instead of cell lines. They found that miR‐221, miR‐222, miR‐181b, miR‐181c, and miR‐128 were significantly downregulated with GBM, while miR‐21 was overexpressed.…”