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Integrative Analysis Reveals Potentially Functional N6-Methylandenosine-Related Long Noncoding RNAs in Colon Adenocarcinoma
Frontiers in Genetics ( IF 2.8 ) Pub Date : 2021-09-17 , DOI: 10.3389/fgene.2021.739344
Xinjie Tan 1 , Qian Li 2 , Qinya Zhang 3, 4 , Gang Fan 5, 6 , Zhuo Liu 7 , Kunyan Zhou 5
Affiliation  

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.



中文翻译:

整合分析揭示了结肠腺癌中与 N6-甲基腺苷相关的长链非编码 RNA 的潜在功能

N6-甲基腺苷 (m6A) 是 mRNA 和非编码 RNA 中最普遍的 RNA 修饰之一。在这项研究中,我们在 mRNA 和蛋白质水平上鉴定了 10 个上调的 m6A 调节因子,以及 2,479 个 m6A 相关的 lncRNA。此外,与 m6A 相关的长链非编码 RNA (lncRNA) 可以清楚地将结肠腺癌 (COAD) 样本分为三个亚型。亚型 2 有近 40% 的样本具有微卫星不稳定性 (MSI),显着高于其他两种亚型。根据这一发现,该亚型的炎症反应相关通路被高度激活。与亚型 1 和 2 相比,亚型 3 的总生存期更短,晚期患者的比例更高。-值 < 0.05)。通路分析表明能量代谢相关通路可能在亚型 3 中被异常激活。 lncRNA 可能与 COAD 的代谢重编程和不利结果有关。在亚型 3 的 m6A 相关 lncRNA 中,有四种被预测为与预后相关。功能推断表明CTD-3184A7.4、RP11-458F8.4和RP11-108L7.15与能量代谢相关通路呈正相关,进一步表明这些lncRNA可能参与能量代谢相关通路。总之,我们进行了系统的数据分析,以确定关键的 m6A 调节因子和 m6A 相关的 lncRNA,

更新日期:2021-09-17
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