Long non-coding RNAs in brain tumors: roles and potential as therapeutic targets

Abstract

Brain tumors are associated with adverse outcomes despite improvements in radiation therapy, chemotherapy, and photodynamic therapy. However, treatment approaches are evolving, and new biological phenomena are being explored to identify the appropriate treatment of brain tumors. Long non-coding RNAs (lncRNAs), a type of non-coding RNA longer than 200 nucleotides, regulate gene expression at the transcriptional, post-transcriptional, and epigenetic levels and are involved in a variety of biological functions. Recent studies on lncRNAs have revealed their aberrant expression in various cancers, with distinct expression patterns associated with their instrumental roles in cancer. Abnormal expression of lncRNAs has also been identified in brain tumors. Here, we review the potential roles of lncRNAs and their biological functions in the context of brain tumors. We also summarize the current understanding of the molecular mechanisms and signaling pathways related to lncRNAs that may guide clinical trials for brain tumor therapy.

Keywords: Brain disease; Genomics; Glioma; LncRNA; Neurodegenerative disease.

Fig. 1

Global trends of brain tumor incidence and death. a Global map showing the incidence and deaths related to brain tumor across the world from 2017 to 2019. b Pie charts present the distribution of incidence and deaths related to brain tumor in major world regions in 2020 for both sexes and all ages. c Bar graph reveals the incidence of brain tumor and corresponding deaths in 2020 in males and females. The data sources and methods used for each world region and detailed condition of the estimates are available online from global health data exchange and GLOBALCAN 2020 at the Global Cancer Observatory (GCO)

Fig. 2

Classification of lncRNAs based on their functional mechanisms. a The multiple functional roles of lncRNAs. In the nucleus, lncRNAs are involved in transcription regulation (activation or repression) via acting as transcription factors, splicing of mRNA, and chromatin modification. In the cytoplasm, they regulate translation by interacting with ribosomes, sponging miRNAs, degrading mRNAs, scaffolding protein interactions, and trafficking transcription factors. Moreover, lncRNAs can be enclosed and released by extracellular vesicles, such as exosomes. b The functional contributions and expression levels of reported lncRNAs in brain tumor

Fig. 3

LncRNAs regulate cellular processes in the tumor cell through diverse signaling pathways. Based on the genetic characteristics and biochemical studies of lncRNAs, it has been proposed that lncRNAs are required for the coordination of several intracellular pathways, such as PI3K-Akt and Wnt pathways. lncRNAs are generated by transcriptional processes when particular signaling pathways are activated. Moreover, expression of lncRNAs is linked to physiological processes of tumor cells