Down-regulation of MicroRNA-126 in Glioblastoma and its Correlation with Patient Prognosis: A Pilot Study

Abstract

Glioblastoma is the most common primary malignant tumor of the adult human brain. Although microRNA-126 (miR-126) has been reported to exhibit expression abnormalities in various types of cancer, to date very few studies have examined changes in miR-126 level in glioblastoma. In this pilot study, we investigated the changes in miR-126 expression in newly-dissected primary glioblastoma to explore possible roles of miR-126 in patient prognosis. Total RNA was extracted from tumoral and adjacent non-cancerous tissues from 14 patients' paired frozen specimens. Using an established quantitative reverse transcriptase-PCR protocol, the levels of miR-126 in glioblastoma and adjacent non-tumor brain tissues were compared against small nucleolar RNA U48 (RNU48) as a reference gene. The expression of miR-126 in glioblastoma samples was significantly lower than in paired non-tumoral controls (p<0.05). Importantly, age-adjusted analyses suggest that glioblastoma patients with higher relative intratumoral miR-126 expression (i.e. 53-79% relative to that of the control tissue; n=7) had significantly improved survival duration than patients whose miR-126 levels were lower (i.e. 12-48%, n=7; stratified log-rank analysis p=0.011 when the dividing threshold was set at ≥51%; total: n=14, male: 8; female: 6). Thus, intraglioblastoma miR-126 may be down-regulated relative to normal tissue and patients with less down-regulation of intratumoral miR-126 expression could have improved postsurgical prognosis. Future clinical studies with larger sample sizes should be performed to validate this observation.

Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines

“…In GBM-derived patient samples, miR126 has been found to be decreased and related to high histopathological grades; while higher intra-tumoural miR126 levels are indicative of significantly improved survival duration, compared to patients with lower miR126 levels [76]. Over-expression of miR126 has been shown to suppress glioma cell proliferation and invasion in vitro [77].…”

Novel Cancer Stem Marker and Its Applicability for Grading Primary Human Gliomas

“…3 Recently, microRNA (miRNA) profiling of glioma biopsies via quantitative PCR has been proposed to aid in glioma grading. 4 , 5 Also, a number of noninvasive techniques have been developed to inform on the status of glioma and its grade. 6 , 7 Modern diagnostic tools are all geared toward accurate assessment of the disease stage, which is clearly required for appropriate choice of the therapeutic options.…”

Differential sequences and single nucleotide polymorphism of exosomal SOX2 DNA in cancer

“…However, in Glioblastoma, miR-126 is downregulated and has a prognostic value. Severely reduced expressions of miR-126 in primary Glioblastoma is attributed to poorer postsurgical survival in comparison with the patients exhibiting less reduction in miR-126 expression [44]. These findings are significant since in our exosomal DNA analysis, we have found that NSC, SH-SY5y, GBM, and CD133 + GBM cell-derived exosomal SOX2 has miR-126 binding sites, both, site-A (1479-1500) and site-B (1744-1764) along with miR-522 binding site (1635-1657) as reported by Otsubo et al The cellular SOX2 DNA for GBM and CD133 + GBM have all the 3 miRNA binding sites, but CD133 + GBM has an SNP in binding site-A (G > A) at position 1495 (Chromosomal position 181713418).…”