N (6)-Methyladenosine Methylomic Landscape of Ureteral Deficiency in Reflux Uropathy and Obstructive Uropathy.
N (6)-Methyladenosine Methylomic Landscape of Ureteral Deficiency in Reflux Uropathy and Obstructive Uropathy.
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反流性尿病和梗阻性尿病中输尿管缺陷的 N6-甲基腺苷甲基化景观
DOI：
10.3389/fmed.2022.924579
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发表时间：
2022
影响因子：
3.9
通讯作者：
Rao, Jia
中科院分区：
文献类型：
--
作者：
Shi, Hua;Xiang, Tianchao;Feng, Jiayan;Yang, Xue;Li, Yaqi;Fang, Ye;Xu, Linan;Qi, Qi;Shen, Jian;Tang, Liangfeng;Shen, Qian;Wang, Xiang;Xu, Hong;Rao, Jia
先天性肾脏和尿路异常（CAKUT）是儿童肾衰竭最常见的原因。RNA表观遗传修饰n6 -甲基腺苷（m6A）甲基化在转录后调节基因表达和功能，最近被发现在器官发育中起关键作用。然而，m6A甲基化是否在CAKUT的发病机制中发挥作用尚不确定。因此，我们旨在探索CAKUT中m6A甲基化的模式。利用m6A- mrna表转录组芯片，我们研究了梗阻性输尿管梗阻性（M组）和原发性膀胱输尿管反流（V组）患儿输尿管组织中的m6A甲基化格局。共有228个参与多种功能相关信号通路的mrna在“V”组和“M”组之间被显著差异甲基化。此外，基于公共数据库预测了215个识别差异甲基化区域的rna结合蛋白。实时荧光定量PCR结果显示，M组m6A读写器（YTHDF1、YTHDF2、YTHDC1、YTHDC2和WTAP） mRNA水平显著升高，m6A擦除器（FTO） mRNA水平显著降低。为了进一步研究差异甲基化基因，我们整合了m6A甲基组和转录组数据，在M/V比较中鉴定出298个差异表达的高甲基化mrna（265个上调，33个下调）和489个差异表达的低甲基化mrna（431个上调，58个下调）。目前的结果强调了m6A甲基化在梗阻性和反流性尿病中的发病机制。
Congenital anomalies of the kidneys and urinary tracts (CAKUT) represent the most prevalent cause for renal failure in children. The RNA epigenetic modification N6-methyladenosine (m6A) methylation modulates gene expression and function post-transcriptionally, which has recently been revealed to be critical in organ development. However, it is uncertain whether m6A methylation plays a role in the pathogenesis of CAKUT. Thus, we aimed to explore the pattern of m6A methylation in CAKUT. Using m6A-mRNA epitranscriptomic microarray, we investigated the m6A methylomic landscape in the ureter tissue of children with obstructive megaureter (M group) and primary vesicoureteral reflux (V group). A total of 228 mRNAs engaged in multiple function-relevant signaling pathways were substantially differential methylated between the “V” and “M” groups. Additionally, 215 RNA-binding proteins that recognize differentially methylated regions were predicted based on public databases. The M group showed significantly higher mRNA levels of m6A readers/writers (YTHDF1, YTHDF2, YTHDC1, YTHDC2 and WTAP) and significantly lower mRNA levels of m6A eraser (FTO) according to real-time PCR. To further investigate the differentially methylated genes, m6A methylome and transcriptome data were integrated to identified 298 hypermethylated mRNAs with differential expressions (265 upregulation and 33 downregulation) and 489 hypomethylated mRNAs with differential expressions (431 upregulation and 58 downregulation) in the M/V comparison. The current results highlight the pathogenesis of m6A methylation in obstructive and reflux uropathy.
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m6A-Atlas：用于解开 N6-甲基腺苷 (m6A) 表观转录组的综合知识库
影响因子：
14.9
作者：
Tang Y;Chen K;Song B;Ma J;Wu X;Xu Q;Wei Z;Su J;Liu G;Rong R;Lu Z;de Magalhães JP;Rigden DJ;Meng J
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Meng J
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3.7
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Christou-Savina S
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7.7
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Guo Q;Kim A;Li B;Ransick A;Bugacov H;Chen X;Lindström N;Brown A;Oxburgh L;Ren B;McMahon AP
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McMahon AP
影响因子：
4.8
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Vaidya, Vishal S.
影响因子：
30.8
作者：
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