Integrative Analysis Reveals Potentially Functional N6-Methylandenosine-Related Long Noncoding RNAs in Colon Adenocarcinoma

• Main Authors: Xinjie Tan, Qian Li, Qinya Zhang, Gang Fan, Zhuo Liu, Kunyan Zhou
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-09-01
• Series: Frontiers in Genetics
• Subjects: N6-methylAdenosine (m6A); colon adenocarcinoma; long noncoding RNAs; metabolic reprogramming; m6A-related lncRNAs
• Online Access: https://www.frontiersin.org/articles/10.3389/fgene.2021.739344/full

N6-methyladenosine (m6A) is one of the most prevalent RNA modifications in mRNA and non-coding RNA. In this study, we identified 10 upregulated m6A regulators at both mRNA and protein levels, and 2,479 m6A-related lncRNAs. Moreover, the m6A-related long noncoding RNAs (lncRNAs) could clearly stratify the colon adenocarcinoma (COAD) samples into three subtypes. The subtype 2 had nearly 40% of samples with microsatellite instability (MSI), significantly higher than the two other subtypes. In accordance with this finding, the inflammatory response-related pathways were highly activated in this subtype. The subtype-3 had a shorter overall survival and a higher proportion of patients with advanced stage than subtypes 1 and 2 (p-value < 0.05). Pathway analysis suggested that the energy metabolism-related pathways might be aberrantly activated in subtype 3. In addition, we observed that most of the m6A readers and m6A-related lncRNAs were upregulated in subtype 3, suggesting that the m6A readers and the m6A-related lncRNAs might be associated with metabolic reprogramming and unfavorable outcome in COAD. Among the m6A-related lncRNAs in subtype 3, four were predicted as prognostically relevant. Functional inference suggested that CTD-3184A7.4, RP11-458F8.4, and RP11-108L7.15 were positively correlated with the energy metabolism-related pathways, further suggesting that these lncRNAs might be involved in energy metabolism-related pathways. In summary, we conducted a systematic data analysis to identify the key m6A regulators and m6A-related lncRNAs, and evaluated their clinical and functional importance in COAD, which may provide important evidences for further m6A-related researches.