Function and prognostic value of N6-methyladenosine-modified RNAs in lung adenocarcinoma.

Abstract

Aberrant regulation of N6-methyladenosine (m6A) modification is reportedly vital for cancer progression, including lung adenocarcinoma (LUAD). However, current studies mainly focus on the function and mechanism of m6A-modified regulators, such as m6A writers (METTL3 and METTL14), erasers (ALKBH5 and FTO), and readers (YTHDF1 and YTHDF2). The landscape, function, and prognostic value of RNAs by m6A-modified have not been fully clarified until now. The present study identified 57 RNAs with significantly different m6A-methylation levels in LUAD tissues using epitranscriptomic microarray analysis. Among the 57 RNAs, 28 and 29 were hypermethylated and hypomethylated, respectively. The m6A-methylation level increased in mRNA and long non-coding RNA (lncRNA) but decreased in small non-coding RNA. After pathway enrichment analyses, RNA metabolism-associated pathways such as nucleotide metabolism were enriched in total and m6A-hypermethylated mRNAs. Furthermore, lncRNA networks were built using miRNet tools, revealing that the immune system was closed to m6A-modified lncRNAs. To evaluate the prognostic value of mRNAs with hypermethylated or hypomethylated, we calculated the risk scores, and constructed signatures to predict the survival time of patients with LUAD using multicox regression analysis. In addition, hypermethylated-mRNA and hypomethylated-mRNA signatures were established. The survival plotter showed that these two signatures effectively predicted the survival time of patients with LUAD. The results of the present study support the evidence for understanding the expression, function, and potential prognostic values of m6A-modified RNAs, possibly promoting effective therapies for patients with LUAD.