Plasma long noncoding RNA MEG3 protected by exosomes as a non-invasive biomarker for diagnosis and patients survival in high-grade gliomas

Background and Aim : Gliomas are the most common malignant primary intracranial tumors of the central nervous system. Despite significant efforts that have gone into glioma research in recent years, the therapeutic efficacy of available treatment options is still limited. Therefore, the non-invasive biomarker with high sensitivity and specificity is required. More and more studies suggest non-coding RNAs to be promising diagnostic biomarkers and therapeutic targets in many cancers, including Glioblastoma. One of the largest groups of these biomarkers is long non-coding RNAs (lncRNAs). MEG3 expression is under epigenetic control Maternally Expressed Gene 3 (MEG3) located at 14q32. This region is the host, two long intergenic RNAs( the MEG3 and MEG8) and one of the largest microRNA clusters in the genome, with 53 miRNAs. Also, miRNAs are involved in the regulation of MEG3 gene expression. Interestingly, the lncRNA MEG3(lnc‐MEG3), as a ceRNA affects various cellular processes such as proliferation, apoptosis, and angiogenesis by sponging miRNAs.This experimental evidence for the first time suggests that MEG3 as a long noncoding RNA is controlled by miR-210 a sponging miRNAs and it is a molecular biomarker for glioma.Methods : The expression levels of MEG3 and miR-210 were detected in 25 patients with high-grade glioma (GBM=25) and 15 head trauma patients, as non-glioma control from March 2017 to June 2018 in the Department of Neurosurgery at Rasoul-e-Akram Hospital by NGS and Real-Time PCR using LNA primer. Moreover, to investigate the prognostic significance of MEG3 in glioma, the Kaplan–Meier method was employed to analyze the association between MEG3 expression level and overall survival rates in GBM patientsResults : Twenty microRNAs were differentially expressed in plasma exosomes from glioblastoma patients relative to trauma. The plasma expression of miR-210 as an oncogenic miR was upregulated in GBM patients compared to trauma controls. This results showed that MEG3 expression was significantly downregulated in glioma patients. Furthermore, for the first time, these findings proved that meg3 expression downregulated and mir-210 upregulated were associated with poor survival in GBM patientsConclusion : These findings indicated a critical role of MEG3 in glioma patients. Furthermore, suggests that plasma exosomal non-coding RNA have potential use as novel biomarkers in GBM patients and it might provide a new target for prognosis and therapeutic intervention in glioma. Furthermore, the present study identified that noncoding RNA plays a vital role in regulating gene expression at the posttranscriptional level and controlling GBM tumoral fate cells in patients. Thus, this research revealed that circulating microRNA can be potentially used as novel biomarkers in the clinical management of glioma patients.

Keywords:

long noncoding RNA , MEG3 , microRNAs , GBM