New insights into long noncoding RNAs and their roles in glioma

Abstract

Glioma is one of the most prevalent types of primary intracranial carcinoma with varying malignancy grades I-IV and histological subtypes, including astrocytomas, glioblastoma multiform (GBM), oligodendrogliomas and mixed tumors. Glioma is characterized by rapid cell proliferation and angiogenesis, and the WHO grade IV glioblastoma, which is highly malignant with poor prognosis because GBM stem-like cells (GSCs) are resistant to conventional therapy and easily recrudescent, accounts for the majority of gliomas. Consequently, investigations exploring the accurate molecular mechanisms and reliable therapeutic targets for gliomas have drawn extensive attention.Based on the increasing amount of functional lncRNAs aberrantly expressed in glioma tissues and cell lines, lncRNAs might be critical for glioma initiation, progression and other malignant phenotypes. This review summarizes the latest insights into the lncRNA field and their functional roles in glioma, therefore evaluating the potential clinical applications of lncRNAs as prospective novel biomarkers and therapeutic targets.

Keywords: Biomarker; Glioma; LncRNAs; Non-coding RNA; Therapeutic targets.

Fig. 1

Schematic representation of lncRNA species and structures. a LncRNAs transcribed from functional DNA element regions: promoter upstream transcript (PROMPTs), enhancer-associated RNA(eRNAs); (b) Mainstream five categories based on genomic location and transcript orientation of lncRNA: (1) sense lncRNAs and (2) antisense lncRNAs, overlapping and transcribed from the same or opposite strand of protein-coding genes, (3) bidirectional lncRNAs, typically transcribed in the opposite direction of its neighboring protein-coding gene (less than 1 kb away) [13], (4) intronic lncRNAs, transcribed entirely from introns [14], (5) intergenic lncRNAs (lincRNAs), transcribed from genomic interval [1]; (c, d) LncRNAs characterized by snoRNA caps: Sno-lncRNAs have snoRNA caps at both ends, while SPA-lncRNAs possess 5’ snoRNA only; (e) LncRNAs characterized by tRNA-like extremities, with the 3′ end alternatively processed by ribonuclease P (RNase P), e.g., MALAT1 and NEAT1_2; (f, g) LncRNAs with close circular structures: derived from back-splicing of exons named circular RNAs, and ciRNAs are produced from intron lariats.

Fig. 2

Functional roles of lncRNAs in glioma malignancy and chemoresistance. LncRNAs contribute to five major malignant phenotypes of glioma by targeting different cell species: general glioma cells, glioma-associated endothelial cells, GBM cells, and GBM stem-like cells. Selected examples of lncRNAs and their molecular partners or genomic targets are shown for stemness, drug resistance, BTB permeability, angiogenesis and motility cancer phenotypes.