Exploring the Roles of lncRNAs in GBM Pathophysiology and Their Therapeutic Potential

Abstract

Glioblastoma (GBM) remains the most devastating primary central nervous system malignancy with a median survival of around 15 months. The past decades of research have not yielded significant advancements in the treatment of GBM. In that same time, a novel class of molecules, long non-coding RNAs (lncRNAs), has been found to play a multitude of roles in cancer and normal biology. The increased accessibility of next generation sequencing technologies and the advent of lncRNA-specific microarrays have facilitated the study of lncRNA etiology. Molecular and computational methods can be applied to predict lncRNA function. LncRNAs can serve as molecular decoys, scaffolds, super-enhancers, or repressors. These molecules can serve as phenotypic switches for GBM cells at the expression and/or epigenetic levels. LncRNAs can affect stemness/differentiation, proliferation, invasion, survival, DNA damage response, and chromatin dynamics. Aberrant expression of these transcripts may facilitate therapy resistance, leading to tumor recurrence. LncRNAs could serve as novel theragnostic or prognostic biomarkers in GBM and other cancers. RNA-based therapeutics may also be employed to target lncRNAs as a novel route of treatment for primary or recurrent GBM. In this review, we explore the roles of lncRNAs in GBM pathophysiology and posit their novel therapeutic potential for GBM.

Diagnosis and Management of Glioblastoma: A Comprehensive Perspective

“…In the continuation of the project, RNA sequencing-based genes proposed genomics signature of life expectancy in patients with glioblastomas [ 80 ]. Transcriptomics and other omics technics proposed prognostic tools for the comprehension of the disease [ 81 , 82 ]. Along with these techniques, liquid chromatography and mass spectrometry analyses from different samples such as CSF (Cerebrospinal fluid), urine, blood or glioblastoma cell lines [ 83 ] have provided a comprehensive view of the altered metabolic pathways in patients with glioblastoma [ 84 , 85 ].…”

DNA Damage Repair Genes and Noncoding RNA in High-Grade Gliomas and Its Clinical Relevance

“…The noncoding RNAs are a diverse group of transcribed RNAs, with long-non coding RNA or lncRNA being the largest sub-type in this category [106]. Long noncoding RNA can regulate gene expression by binding to the gene's promoter and recruiting activators or repressors, or chromatin modifiers and activating or repressing transcription, respectively [106,107]. Alternatively, they can work as antisense and bind to the transcripts, thereby inhibiting translation or destabilizing the transcript.…”

“…It is a potential target for therapeutic interventions. Their expression pattern in response to chemotherapeutic treatment has prognostic value and serves as predictive biomarkers [106,107].…”

Long, Noncoding RNA Dysregulation in Glioblastoma

“…HOTAIRM1 is located between the HOXA1 and HOXA2 genes and is normally expressed in cells of the myeloid lineage [ 98 , 99 ]. In GBM, HOTAIRM1 is upregulated and promotes proliferation, migration, and invasion of tumor cells via several mechanisms.…”