Transcriptome-wide analysis of glioma stem cell specific m6A modifications in long-non-coding RNAs

Abstract

The interest in chemical RNA modifications is rapidly growing in the field of molecular biology. Dynamic and reversible alterations of N6-methyladenosine (m6A) RNA modification are responsible for a platter of structural and functional changes in healthy and cancerous cell states. Although many studies reported the link between tumor initiation/progression and m6A modulators, there are few studies exploring transcriptome-wide m6A profile of non-coding RNAs. The aim of current study was to identify glioma stem cell (GSC) specific m6A landscape of long non-coding RNAs (lncRNAs) applying MeRIP-seq approach. MeRIP-seq analysis assigned 77.9% of m6A peaks to mRNAs and 8.16% to lncRNAs. GSCs and differentiated cells showed 76.4% conservation of m6A peaks, while 19.4% were unique to GSCs. Seven novel GSC-specific m6A modified lncRNAs were identified: HRAT92, SLCO4A1-AS1, CEROX1, PVT1, AGAP2-AS1, MIAT, and novel lncRNA gene ENSG00000262223. Analysis disclosed a strong negative correlation between lncRNAs m6A modification rate and expression. MeRIP-seq analysis revealed m6A modifications on previously reported glioma-associated lncRNAs: LINC000461, HOTTIP, CRNDE, TUG1, and XIST. Moreover, current study disclosed that most highly m6A modified lncRNAs primarily contain m6A modifications close to 3′ and 5′ ends. Our results provide basis and insight for further studies of m6A modifications in non-coding transcriptome of GSCs.

N6-methyladenosine-modified lncRNA and mRNA modification profiles in cerebral ischemia-reperfusion injury

“…The process of methylation is reversible, and the level of RNA m 6 A methylation modification is regulated by methyltransferases and demethylases ( Roundtree et al, 2017 ). Several current studies suggest that lncRNAs may regulate tumor growth through m 6 A modification in cancer ( Steponaitis et al, 2022 ). Unfortunately, the role of m 6 A-related lncRNAs and mRNAs in CIRI has not been elucidated.…”

A TGF‐β signaling‐related lncRNA signature for prediction of glioma prognosis, immune microenvironment, and immunotherapy response

“…In the TCGA cohort of this study, its high expression suggested a poor prognosis in glioma, which was inconsistent with the results in the CGGA cohort. However, based on its prevalence as an oncogene in previous bioinformatics analysis related‐literature reports, 71,72 combined with the results validated in our subsequent experiments, AGAP2‐AS1 is considered to be a risk lncRNA for glioma, and the result of CGGA is considered to be confounded by its small sample size. Furthermore, it affected the immune microenvironment and was associated with sensitivity to immunotherapy and chemotherapy.…”

Hypoxia triggers cardiomyocyte apoptosis via regulating the m6A methylation-mediated LncMIAT/miR-708-5p/p53 axis

“…To investigate the effect of ALKBH5 on m 6 A methylation in hypoxic cardiomyocytes, the ALKBH5 level was subsequently measured, which exhibited a significant increase compared with the normoxic control. A recent study suggested that m 6 A methylation could influence the expression of LncMIAT [ 46 ]. Notably, intensive studies showed that ALKBH5 can regulate the m 6 A methylation of lncRNAs, further affecting their expression and function [ [47] , [48] , [49] ].…”