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Main text N-methyladenosine (mA) has become a critical internal RNA modification, and it plays important roles in the development and progression of cancer [1]. mA has also been found in diverse non-coding RNAs, such as microRNAs and long noncoding RNAs (lncRNAs) [2]. LncRNAs comprise a large class of RNA transcripts and are critical regulators of gene expression. The regulatory effectiveness of lncRNAs is closely associated with spatial expression, whose dysregulation often influences cancer development and progression [3]. For these reasons, global characterization of lncRNA spatial expression across tissues or cancers could improve our understanding of lncRNA functions. Recently, LncRNA Spatial Atlas (LncSpA) and landscape of mA have been proposed as valuable resources to understand lncRNA and mA regulatory functions across different tissues [4, 5]. However, we still lack understanding of the distribution and functions of mA modification in lncRNAs, particularly the tissue-elevated (TE) lncRNAs. In this study, we aimed to systematically characterize the distribution and clinical relevance of mA-related TE lncRNAs across tissues and cancer types. We found that TE lncRNAs were found to be regulated by mA modification across tissues, particular brain tissues. We also investigated the correlation between expression of mA regulators and TE lncRNAs, and found that numbers of mA-related TE lncRNAs were associated with expression of mA regulators. We assessed the clinical prognostic values of mA-regulated TE lncRNAs. We identified several mA-related TE lncRNAs as potentially useful markers for prognostic stratification. Our analysis highlights the importance of mA modification in the regulation of lncRNA expression and helps bridge the knowledge gap between lncRNA expression and phenotypes.

Pan-cancer characterization of expression and clinical relevance of m6A-related tissue-elevated long non-coding RNAs