The Gastroenterology Tumor and Microenvironment Laboratory, Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu Medical College, Chengdu 610041, Sichuan, PR China.
Aging (Albany NY). 2021 Jan 20;13(3):4182-4198. doi: 10.18632/aging.202383.
Long non-coding RNAs (lncRNAs) and their N6-methyladenosine (M6A) modifications are involved in cancer occurrence and development.
lncRNA M6A modification in colorectal cancer (CRC) was comprehensively analyzed for the first time.
M6A levels of lnRNAs in CRC tissues were higher than those in tumor-adjacent normal tissues. A total of 8,332 M6A peaks were detected in 6,690 lncRNAs in CRC tissues. Approximately 91% of the modified lncRNAs had unique M6A modification peaks. A total of 383 lncRNAs were differentially methylated in CRC, of which 48.24% had a length of 1-1,000 bp. Most of these were located on chromosomes 1, 2, 7, 11, 16 and 19; 42.3% were within a sense-overlapping exon. RNA sequencing identified 163 differentially expressed lncRNAs in CRC. GO and KEGG analyses revealed that genes near differentially-methylated or -expressed lncRNAs were associated with CRC occurrence and development. Methylation was positively correlated with lncRNA expression levels in CRC and tumor-adjacent normal tissues. More unmethylated than M6A methylated lncRNA molecules were detected. A competing endogenous RNA (ceRNA) and lncRNA-mRNA expression-regulation network revealed a regulatory relationship between lncRNAs, microRNAs (miRNAs), and mRNAs.
The findings may help improve our understanding of lncRNA function in colorectal cancer.
长链非编码 RNA（lncRNA）及其 N6-甲基腺苷（M6A）修饰参与癌症的发生和发展。
首次全面分析结直肠癌（CRC）中的 lncRNA M6A 修饰。
CRC 组织中的 lncRNA M6A 水平高于肿瘤邻近正常组织。在 CRC 组织中检测到 6690 个 lncRNA 中的 8332 个 M6A 峰。大约 91%的修饰 lncRNA 具有独特的 M6A 修饰峰。CRC 中共有 383 个 lncRNA 发生差异甲基化，其中 48.24%的长度为 1-1000bp。这些 lncRNA 大部分位于染色体 1、2、7、11、16 和 19 上；42.3%位于顺式重叠外显子内。RNA 测序鉴定出 CRC 中 163 个差异表达的 lncRNA。GO 和 KEGG 分析表明，差异甲基化或表达的 lncRNA 附近的基因与 CRC 的发生和发展有关。CRC 和肿瘤邻近正常组织中，甲基化与 lncRNA 表达水平呈正相关。未甲基化的 lncRNA 分子比 M6A 甲基化的 lncRNA 分子多。竞争性内源性 RNA（ceRNA）和 lncRNA-mRNA 表达调控网络揭示了 lncRNA、微小 RNA（miRNA）和 mRNA 之间的调控关系。
这些发现可能有助于提高我们对结直肠癌中 lncRNA 功能的理解。
