Recent insights into the microRNA-dependent modulation of gliomas from pathogenesis to diagnosis and treatment

Abstract

Gliomas are the most lethal primary brain tumors in adults. These highly invasive tumors have poor 5-year survival for patients. Gliomas are principally characterized by rapid diffusion as well as high levels of cellular heterogeneity. However, to date, the exact pathogenic mechanisms, contributing to gliomas remain ambiguous. MicroRNAs (miRNAs), as small noncoding RNAs of about 20 nucleotides in length, are known as chief modulators of different biological processes at both transcriptional and posttranscriptional levels. More recently, it has been revealed that these noncoding RNA molecules have essential roles in tumorigenesis and progression of multiple cancers, including gliomas. Interestingly, miRNAs are able to modulate diverse cancer-related processes such as cell proliferation and apoptosis, invasion and migration, differentiation and stemness, angiogenesis, and drug resistance; thus, impaired miRNAs may result in deterioration of gliomas. Additionally, miRNAs can be secreted into cerebrospinal fluid (CSF), as well as the bloodstream, and transported between normal and tumor cells freely or by exosomes, converting them into potential diagnostic and/or prognostic biomarkers for gliomas. They would also be great therapeutic agents, especially if they could cross the blood–brain barrier (BBB). Accordingly, in the current review, the contribution of miRNAs to glioma pathogenesis is first discussed, then their glioma-related diagnostic/prognostic and therapeutic potential is highlighted briefly.

microRNAs (miRNAs) in Glioblastoma Multiforme (GBM)—Recent Literature Review

“…The miRNA profile in GBM indicates the stage of the disease and can also facilitate the prognosis and selection of appropriate therapy. Based on the level of individual miRNAs, the miRNAs with the highest prognostic value for GBM were selected [ 72 ], indicating that that the diagnosis of GBM is also possible on the basis of the analysis of miRNA from the blood and cerebrospinal fluid of patients [ 73 , 74 , 75 ]. Functional analysis of individual GBM-specific miRNAs indicates that they can act as both oncogenes and tumor suppressors, are responsible for developing resistance to chemotherapy and radiotherapy, stimulate neo-angiogenesis and cell proliferation, and regulate the cell cycle and apoptosis [ 76 , 77 , 78 , 79 , 80 ] ( Table 2 ).…”

The landscape of exosomal non-coding RNAs in breast cancer drug resistance, focusing on underlying molecular mechanisms

“…MiRNAs are small single-stranded RNA molecules (20–24 nucleotides) primarily contributing to post-transcriptional gene modulation through binding to the target gene’s 3′-untranslated region (3′UTR) to suppress the translation ( Ruan and Ouyang, 2009 ; Sana et al, 2012 ; Bahmyari et al, 2021 ; Mafi et al, 2022 ). Subcellular localization of miRNAs, the affinity of miRNA-related interconnections, and the number of target mRNAs and miRNAs influence the miRNA–target gene interactions ( O'Brien et al, 2018 ).…”

The Role of miRNAs in the Progression and Prognosis of Gliomas

“…MiRNAs can exhibit either pro-apoptotic or anti-apoptotic characteristics. Those that target genes that promote apoptosis are frequently observed in glial tumors, and it is believed that miR-21, due to its anti-apoptotic nature, may have micro-oncogenic properties [23]. In GBM cells and malignant brain tissues, miR-21 expression is significantly elevated.…”

“…In GBM, miRNAs act on pre-altered genetic pathways, such as the wingless/integrated (WNT) pathway, P53 pathway, and retinoblastoma (RB) pathway, leading to increased proliferation rate, decreased apoptosis, angiogenesis, de-differentiation, and metastasis [23].…”