LncRNAs associated with glioblastoma: From transcriptional noise to novel regulators with a promising role in therapeutics

Abstract

Glioblastoma multiforme (GBM) is the most widespread and aggressive subtype of glioma in adult patients. Numerous long non-coding RNAs (lncRNAs) are deregulated or differentially expressed in GBM. These lncRNAs possess unique regulatory functions in GBM cells, ranging from high invasion/ migration to recurrence. This review outlines the present status of specific involvement of lncRNAs in GBM pathogenesis, with a focus on their association with key molecular and cellular regulatory mechanisms. Also, we highlighted the potential of different novel RNA-based strategies that may be beneficial for therapeutic purposes. lncRNAsDepending on the genomic location and with respect to neighboring protein-coding genes, lncRNAs can be sense, antisense, intronic, intergenic, and bidirectional. Sense and antisense are transcribed in the same or opposite direction of protein-coding gene strands. Bidirectional lncRNAs are transcribed in the opposite direction of their neighboring protein-coding gene (<1 kb away). Intronic lncRNAs are transcribed completely from the introns of the protein-coding gene, while intergenic lncRNAs are transcribed from different genomic locations. 10 The activity of lncRNAs depends on its subcellular localization, allowing division of lncRNAs into nuclear or cytoplasmic subgroups. 11 A gene transcriptional status can be regulated by transcriptional interference and chromatin remodeling acquired from lncRNA located in the nuclear region. 12,13 In contrast, lncRNAs that are exported to the cytoplasm serve as mediators for RNA processing and can affect mRNA stability or regulate protein function. 14 lncRNAs can interact with RNA, proteins, and DNA via different modes of molecular mechanisms such as signaling, decoy, guide, scaffold, and miRNA sponge. lncRNAs can function as a signaling molecule for any biological condition and are capable of regulating the expression of genes concerning a specific response; as a decoy

Prognostic Utility of LncRNAs (LINC00565 and LINC00641) as Molecular Markers in Glioblastoma Multiforme (GBM)

“…The recent researches on lncRNAs have reported that intergenic non-coding RNA can act as endogenous miRNA sponge in cancer cells to promote tumor development. 27 Hence molecular classi cation based on expression of lncRNAs may direct for gene therapy and may aid to a better procedure for targeted therapy selection. 28,29 In the current prospective study, two lncRNAs were investigated (lncRNA565 and lncRNA641) in blood samples from GBM patients and a healthy control group were recruited.…”

Prognostic Roles of LncRNA XIST and Its Potential Mechanisms in Human Cancers: A Pan-Cancer Analysis

“…LncRNAs were initially described as mere "transcriptional noise", but now increasing studies have demonstrated that LncRNAs act as critical modulators in a variety of physiological activities [29]. However, only a relatively limited number of LncRNAs have been confirmed to have critical biological functions, and molecular mechanisms of most LncRNAs have not been illustrated [30].…”

Transforming Growth Factor-Beta-Regulated LncRNA-MUF Promotes Invasion by Modulating the miR-34a Snail1 Axis in Glioblastoma Multiforme

“…LncRNAs interact with proteins or other non-coding RNAs to regulate gene expression in cis and trans to modulate cancer phenotypes (10,14). Several differentially expressed lncRNAs have been identified in GBM, which regulate various aspects of GBM pathology (15)(16)(17)(18)(19)(20). TGF-b-regulated lncRNAs modulate invasion, metastasis, and EMT in various cancers (21).…”