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Acta Academiae Medicinae Sinicae

Abbreviation (ISO4): Acta Academiae Medicinae Sinicae      Editor in chief: Xuetao CAO

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Acta Academiae Medicinae Sinicae >

2025 , Vol. 47 >Issue 1: 86 - 94

DOI: https://doi.org/10.3881/j.issn.1000-503X.16053

Review Articles

Current Progress of 5-Methylcytosine RNA Methylation in Non-Neoplastic Kidney Diseases

  • ZHANG Chen ,
  • ZHAO Zixia ,
  • WU Si ,
  • LUAN Junjun ,
  • ZHOU Hua
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  • Department of Nephrology,Shengjing Hospital of China Medical University,Shenyang 110000,China
ZHOU Hua Tel:024-96615-25211,E-mail:

Received date: 2024-02-28

  Online published: 2025-03-12

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Abstract

RNA methylation is a key process in the epigenetic regulation of post-transcriptional gene expression.5-Methylcytosine(m5C)is a type of RNA methylation,commonly existing in eukaryotic mRNA and non-coding RNAs.It mainly regulates transfer RNA stability,ribosomal RNA assembly,and mRNA translation,stability,and translation.RNA methylation is dynamically reversible and regulated by methyltransferase,demethylase,and methylation recognition protein.It has been confirmed that aberrant m5C RNA methylation is involved in the pathogenesis of non-neoplastic kidney diseases.This article summarizes the current progress of m5C RNA methylation associated with non-neoplastic acute and chronic kidney diseases,aiming to provide potential targets for the diagnosis and treatment of such diseases.

Key words： epigenetics; RNA methylation; RNA; 5-methylcytosine; kidney diseases

Cite this article

ZHANG Chen , ZHAO Zixia , WU Si , LUAN Junjun , ZHOU Hua . Current Progress of 5-Methylcytosine RNA Methylation in Non-Neoplastic Kidney Diseases[J]. Acta Academiae Medicinae Sinicae, 2025 , 47(1) : 86 -94 . DOI: 10.3881/j.issn.1000-503X.16053

非肿瘤性肾脏疾病按起病的急缓可分为急性肾损伤(acute kidney injury,AKI)和慢性肾脏病(chronic kidney disease,CKD)。AKI是常见的危重病症之一,具有死亡率高、住院时间长和并发症严重的特点[1]。目前,中国CKD患病率为8.2%~10.8%[2-3],全球患病率为9.1%[4],预计到2040年CKD将成为全球第五大死因[5],防治形势十分严峻。然而,非肿瘤性肾脏疾病的发病机制仍不清楚,揭示其发病的分子机制对于疾病的防控具有重要意义。RNA甲基化修饰是基因表达转录后水平表观遗传学调控的关键过程,包括N6-甲基腺苷(N6-methyladensine,m6A)、5-甲基胞嘧啶(5-methylcytosine,m5C)和N1-甲基腺苷等修饰,异常的表观遗传调控机制与非肿瘤性肾脏疾病的发生有关[6]。本文介绍了m5C RNA甲基化及其与非肿瘤性肾脏疾病发病机制相关的研究进展,以期为m5C RNA甲基化在肾脏疾病领域的研究提供新思路。

1 m5C RNA甲基化

1.1 m5C RNA甲基化概述

20世纪70年代,m5C首次被发现。m5C RNA甲基化是发生在RNA胞嘧啶第5位碳原子上的甲基化修饰,是真核生物mRNA和多种非编码RNA中常见的一种转录后修饰,包括转运RNA(transfer RNA,tRNA)、核糖体RNA(ribosomal RNA,rRNA)、长链非编码RNA(long noncoding RNA,lncRNA)、核小RNA(small nuclear RNA,snRNA)、微小RNA(micro-RNA,miRNA)和增强子RNA(enhancer RNA,eRNA)等[7]。在tRNA中,m5C RNA甲基化可优化密码子-反密码子配对,调节应激反应,控制翻译效率和准确性[8-9]。在rRNA中,m5C RNA甲基化与rRNA-tRNA-mRNA复合物的结构稳定性有关[10]。在真核生物的mRNA中,m5C RNA甲基化具有调节mRNA稳定性、剪切和核-细胞质穿梭[11⇓-13],参与DNA损伤修复[14]、细胞增殖迁移[15]和干细胞的发育分化[16]等生物学过程的作用。m5C RNA甲基化异常与多种疾病的发生发展有关,包括动脉硬化[17]、自身免疫性疾病[18]和癌症[19]等。

1.2 m5C RNA甲基化相关酶及其功能

m5C RNA甲基化修饰过程是动态可逆的,受m5C RNA甲基化相关酶的调控。这些酶包括甲基转移酶(编码器)、去甲基化酶(消码器)和甲基化识别蛋白(读码器)[20],主要调控RNA的稳定性、翻译、转录、出核和切割等生理过程(表1)[8,10-11,14-15,17,19,21⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓-42]。
表1 m5C RNA甲基化相关酶及其作用机制
分类 酶 靶RNA 作用机制 参考文献
编码器 NSUN1 28S rRNA 调节pre-rRNA加工,维持核仁小核糖核蛋白复合物的稳定性 [23]
NSUN2 mRNA 调节ALYREF的核胞质穿梭、ALYREF与mRNA结合力和mRNA核输出 [11]
促进mRNA翻译,包括通过YBX1促进mRNA翻译 [17,24]
通过YBX1维持mRNA稳定性 [19]
降低mRNA稳定性 [25]
tRNA 增加tRNA稳定性和总体蛋白质合成率 [8,26]
mt-tRNA、miRNA和lncRNA 机制不清 [27]
NSUN3 mt-tRNAMet 促进线粒体翻译,维持线粒体功能 [28]
NSUN4 12S rRNA 促进线粒体核糖体组装,在线粒体核糖体生物发生中发挥作用 [29]
mRNA NSUN4与Mettl3形成复合物,通过募集YTHDF2和真核翻译延伸因子1α-1,
促进mRNA翻译		 [30]
NSUN5 28S rRNA 维持三级复合物rRNA-tRNA-mRNA的结构稳定性,调节蛋白质合成 [10,31]
mRNA 维持mRNA翻译和稳定性,影响翻译效率 [32-33]
NSUN6 mRNA 促进mRNA翻译,可能与翻译终止相关 [34-35]
tRNA 机制不清 [36]
NSUN7 eRNA 增强eRNA的稳定性 [37]
mRNA 维持mRNA稳定性 [38]
DNMT2 tRNA 调节tRNA的稳定性和识别临近密码子 [33⇓-35]
mRNA 在DNA损伤中促进同源重组,RAD52可能作为读码器发挥作用 [14-15]
消码器 TET1~3 mRNA 羟甲基胞嘧啶有利于mRNA的转录 [39]
影响RNA双链的形成 [40]
tRNA 促进翻译 [40]
ALKBH1 tRNA 促进线粒体翻译,维持线粒体功能 [21,28]
mRNA 机制不清 [21]
读码器 ALYREF mRNA 参与mRNA核胞质穿梭和mRNA核输出 [11]
维持mRNA稳定性 [42]
YBX1 mRNA 维持mRNA稳定性 [23]
促进mRNA翻译 [24]
YTHDF2 mRNA 促进mRNA降解 [22]

注:m5C:5-甲基胞嘧啶;NSUN:NOL1/NOP2/SUN结构域;DNMT2:DNA甲基转移酶同源物2;TET:甲基胞嘧啶双加氧酶;ALKBH1:α-酮戊二酸依赖性双加氧酶ABH1;ALYREF:Aly/REF输出因子;YBX1:Y-box结合蛋白1;YTHDF2:YTH结构域家族2;rRNA:核糖体RNA;tRNA:转运RNA;mt-tRNA:线粒体转运RNA;miRNA:微小RNA;lncRNA:长链非编码RNA;eRNA:增强子RNA

m5C甲基转移酶以S-腺苷甲硫氨酸为甲基供体,将甲基转移至胞嘧啶上形成m5C,因此被称为催化m5C RNA甲基化的编码器。人类m5C编码器主要包括NOL1/NOP2/SUN结构域(NOL1/NOP2/SUN domain,NSUN)家族蛋白和DNA甲基转移酶同源物2(DNA methyltransferase homolog 2,DNMT2)[43]。NSUN家族蛋白包括NSUN1至NSUN7。NSUN家族蛋白和DNMT家族蛋白都含有保守基序Ⅳ和Ⅵ。NSUN家族蛋白中基序Ⅵ的半胱氨酸通过亲核攻击靶向RNA胞嘧啶C6,同时基序Ⅳ的脯氨酸和天冬氨酸侧链与氢原子相互作用活化核碱基,并接受S-腺苷甲硫氨酸的甲基形成m5C[44]。在上述m5C编码器中,NSUN2、NSUN4、NSUN5、NSUN6、NSUN7和DNMT2参与催化mRNA甲基化。
m5C消码器包括甲基胞嘧啶双加氧酶(ten-eleven translocation,TET)家族蛋白和α-酮戊二酸依赖性双加氧酶ABH1(α-ketoglutarate-dependent dioxygenase ABH1,ALKBH1)。TET家族蛋白包括TET1、TET2和TET3,最初主要作为DNA去甲基化酶被研究,其催化反应需要Fe2+和α-酮戊二酸作为辅助因子[45]。作为生成hm5C和f5C的主要RNA去甲基化酶,ALKBH1具有对tRNA和mRNA的m5C氧化作用[21]。
m5C读码器包括Aly/REF输出因子(Aly/REF export factor,ALYREF)、Y-box结合蛋白1(Y-box binding protein 1,YBX1)和YTH结构域家族2(YTH domain-containing family 2,YTHDF2)[46],能够特异性识别和结合RNA m5C甲基化位点。ALYREF是在细胞核中被发现的第1个mRNA读码器,具有关键的m5C识别位点。ALYREF能识别mRNA转录本的m5C位点,在mRNA出核过程中发挥作用[11]。YBX1是高度保守的冷休克结构域蛋白家族成员,在细胞质和细胞核内具有多种功能[16]。YBX1与DNA结合,发挥转录因子的作用。YBX1与多种mRNA相互作用,有效地发挥帽依赖性mRNA稳定剂的作用。磷酸化的YBX1是核糖核酸蛋白的关键调节因子;非磷酸化的YBX1与无翻译活性的信使核糖核蛋白体结合,抑制内部核糖体依赖性的mRNA翻译,一旦非磷酸化YBX1的S102位点被磷酸化,不仅其mRNA结合能力减弱,导致mRNA翻译启动,而且其易位至细胞核,引起YBX1相关基因的表达增加[47]。YTHDF2属于YTH结构域蛋白家族,为多功能甲基化识别蛋白,可识别m6A、m5C和m1A甲基化修饰位点,主要促进mRNA降解[22]。研究显示,YTHDF2通过疏水袋中的保守残基Trp432(色氨酸)特异性识别并结合RNA中的m5C,从而发挥m5C读码器的功能[48]。

2 m5C RNA甲基化与非肿瘤性肾脏疾病发病的关系

目前,m5C RNA甲基化在非肿瘤性肾脏疾病发病机制方面的研究尚处于起步阶段,以下主要介绍m5C RNA甲基化相关酶与急慢性肾脏疾病发病机制相关的研究进展(表2)[49⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓-66]。
表2 m5C RNA甲基化相关酶对肾脏疾病的作用及其机制
肾脏疾病或模型 酶 作用及机制 参考文献
缺血再灌注诱导的AKI TET2↓ 抑制炎症,起保护作用 [49]
缺血再灌注诱导的AKI TET1/TET2↓ 影响启动子去甲基化,调控基因的表达 [50]
缺血再灌注/顺铂/肾移植/脓毒症诱导的AKI TET2↓ 通过PPAR信号通路调节代谢和炎症反应,起保护作用 [51]
缺血再灌注诱导的AKI TET3↓ 肼苯哒嗪诱导TET3表达,RASAL1启动子去甲基化,减轻纤维化 [52]
肝纤维化相关AKI YBX1↓ YBX1与CXCL1启动子结合,抑制CXCL1转录 [53]
钙调神经磷酸酶抑制剂肾毒性 YBX1↑ 蛋白激酶B/细胞外调节蛋白激酶催化YBX1在Ser102位点的磷酸化,YBX1稳定COL1A mRNA,促进纤维化 [54]
CKD YBX1 YBX1与TGF-β1 mRNA 5’非编码区结合,促进TGF-β1表达 [55]
CKD YBX1 反式激活MMP-2,上调MMP-2转录,活化肾小球系膜细胞 [56]
UUO YBX1↑ YBX1与IHG-1结合,促进TRAP1降解 [57]
UUO 胞质YBX1↑ 稳定COL1A1 mRNA,促进纤维化,HSc025增加YBX1核移位,抑制COL1A1转录 [58]
UUO YBX1↑ 在单核细胞中,YBX1调节IL-10等抗炎细胞因子 [60]
UUO TET2↑ HIF-1α上调,触发代谢重塑,TET2上调,α-平滑肌肌动蛋白启动子去甲基化,促进纤维化 [63]
UUO TET3↓ RASAL1启动子高甲基化,RASAL1下调,促进纤维化,BMP7可上调TET3 [65]
UUO TET3 基于CRISPR/Cas9的基因特异性双加氧酶,靶向激活RASAL1和Klotho,减轻纤维化 [66]
DKD TET1↓ 上游激活蛋白1抑制TET1,TET1促进核因子E2相关因子2转录 [61]
DKD TET1/TET3↓ 肥胖和糖尿病在雌性小鼠中负向调节肾小球TET家族蛋白表达 [62]
DKD TET2↑ 通过DNA去甲基化上调TGFβ1,促进DKD [64]
DKD YBX1↓ miR-216a靶向YBX1,YBX1下调导致Tsc-22上调,促进COL1A2表达 [59]

注:AKI:急性肾损伤;CKD:慢性肾脏病;UUO:单侧输尿管梗阻;DKD:糖尿病肾病;PPAR:过氧化物酶体增殖物激活受体;TGF-β1:转化生长因子-β1;MMP-2:基质金属蛋白酶-2;IHG-1:高糖诱导蛋白-1;IL-10:白细胞介素-10;HIF-1α:缺氧诱导因子-1α;BMP7:骨形态蛋白7;CRISPR/Cas9:成簇规律间隔短回文重复序列及其相关蛋白9

2.1 AKI

在AKI发病过程中,m5C消码器TET发挥着重要作用。研究显示AKI患者肾穿刺活检标本和多种AKI小鼠模型(包括缺血再灌注、顺铂、肾移植和脓毒症诱导的AKI小鼠模型)中TET2的表达均下降。与野生型小鼠相比,TET2敲除小鼠的肾脏损伤更严重,AKI标志物水平更高,炎症反应更严重,而TET2过表达质粒能减轻肾损伤;TET2可能通过过氧化物酶体增殖物激活受体(peroxisome proliferators-activated receptor,PPAR)信号通路调节代谢和炎症反应,从而减轻AKI造成的肾脏损伤[49⇓-51]。Huang等[50]研究发现AKI小鼠模型肾组织中DNA 5-羟甲基胞嘧啶水平降低,提示TET可能通过调节启动子去甲基化,进而调控靶基因表达。在缺血再灌注诱导的AKI小鼠模型中,TET3的表达亦下调,而低剂量肼苯哒嗪可诱导TET3表达,催化RASAL1启动子去甲基化,进而减轻肾脏纤维化,因此,TET3是独立于降压机制的肾功能保护因子,其可能在AKI向CKD的进展过程中发挥重要作用[52]。上述结果提示,AKI时存在TET表达下调的现象,TET2在AKI患者和4种AKI小鼠模型中均表达下调;而上调TET可减轻AKI,并对AKI发挥保护作用。目前的研究仅表明TET促进DNA去甲基化,其作为m5C消码器参与AKI发病的机制还有待进一步探究。
与肝硬化相关的AKI中,m5C读码器YBX1与肝肾串扰有关。与野生型小鼠相比,杂合YBX1基因敲除小鼠的肾脏对趋化因子CXCL1反应性增强,肾损伤更严重。YBX1可能通过与CXCL1启动子结合,抑制CXCL1基因转录,在肝纤维化和肝肾串扰中发挥作用[53]。

2.2 CKD

CKD是由各种原因引起的肾脏结构或功能异常,肾脏纤维化是CKD发展至终末期肾病的共同病理过程。m5C读码器YBX1与肾间质纤维化密切相关。YBX1在钙调神经磷酸酶抑制剂处理的肾小球系膜细胞中表达上调,蛋白激酶B/细胞外调节蛋白激酶催化YBX1的Ser102位点磷酸化,磷酸化的YBX1通过稳定COL1A mRNA导致胶原产生增加,进而促进肾脏纤维化[54]。在人近端肾小管上皮细胞中,YBX1通过与转化生长因子-β1(transforming growth factor-β1,TGF-β1)mRNA 5’非编码区的高亲和位点结合,促进TGF-β1表达,参与CKD进展[55]。在大鼠肾小球系膜细胞中,YBX1作为转录因子反式激活基质金属蛋白酶2(matrix metallopeptidase 2,MMP-2),导致肾小球系膜细胞活化[56]。通过单侧输尿管结扎建立的单侧输尿管梗阻(unilateral ureteral obstruction,UUO)动物模型,是一种被广泛应用的肾小管间质纤维化动物模型。YBX1在UUO模型中表达增加,Bhreathnach等[57]发现YBX1通过与高度保守的线粒体蛋白高糖诱导蛋白-1(induced in high glucose-1,IHG-1)结合,促进肾小管间质纤维化。Wang等[58]研究发现,在杂合YBX1敲除(Ybx1+/-)后,UUO肾脏纤维化模型小鼠的肾小管损伤、免疫细胞浸润和肾脏纤维化明显减少;在输尿管梗阻期,位于细胞质的YBX1通过稳定COL1A mRNA促进纤维化,小分子化合物HSc025通过增加细胞核内YBX1浓度,增加了与COL1A启动子结合的YBX1,抑制COL1A转录,从而减轻输尿管梗阻后的纤维化。这提示YBX1磷酸化及其亚细胞定位决定了其对肾脏纤维化的影响,诱导YBX1向核内穿梭可能是肾脏疾病抗纤维化治疗的新策略。与促进UUO肾小管间质纤维化不同,YBX1对糖尿病肾病(diabetic kidney disease,DKD)表现出保护作用。细胞外基质蛋白沉积和TGF-β诱导的肾系膜细胞增生是DKD的标志性特征。在DKD模型小鼠系膜细胞中,TGF-β上调miR-216a水平,miR-216a靶向抑制YBX1,导致YBX1下调,YBX1可与Tsc-22 mRNA结合,YBX1下调导致Tsc-22 mRNA从P体释放增加,Tsc-22上调,从而增加COL1A2的表达,促进纤维化[59]。此外,YBX1还与炎症进程有关。Bernhardt等[60]研究证实,特异性敲除单核/巨噬细胞的YBX1基因后,UUO模型小鼠出现炎症细胞浸润增加,肾小管间质纤维化加重,同时YBX1缺陷的巨噬细胞出现细胞极化和功能异常,包括增殖和一氧化氮产生减少,吞噬活性丧失,在炎症刺激时白细胞介素-10和趋化因子CCL5表达未上调。Rana等[67]发现YBX1还参与了肾小球小管串扰,当YBX1由肾小球足细胞生理性分泌后,与肾小管Toll样受体4作用,抑制核苷酸结合寡聚化结构域样受体3炎症小体的激活。综上,YBX1在CKD纤维化和炎症中扮演着复杂的角色。YBX1作为一种多功能蛋白,在细胞核中可与DNA结合,发挥转录因子的作用,在细胞质内也可与RNA结合,在非肿瘤性肾脏疾病中的作用与其亚细胞定位有关。但是YBX1的作用机制是否与m5C RNA甲基化有关,是否作为m5C读码器发挥作用需要进一步研究证实。
m5C消码器TET在CKD的发生发展中发挥着重要作用。DKD属于继发性肾小球疾病,是糖尿病最常见的微血管并发症之一。Tan等[61]发现,在DKD模型大鼠和高糖诱导的人肾小球系膜细胞中,TET1表达减少,而上调TET1可通过抑制系膜细胞活性、纤维化和炎症,改善肾损伤;激活蛋白1能够降低高糖诱导的人肾小球系膜细胞表达TET1,从而抑制核因子E2相关因子2(nuclear factor E2-related factor-2,Nrf2)的转录,且激活蛋白1/TET1轴可通过调节Nrf2/抗氧化反应元件通路活性影响DKD。在另一项研究中,肥胖和糖尿病负向调控雌性小鼠肾小球细胞表达TET1和TET3,提示DKD表观遗传学机制可能存在性别差异[62]。然而,与TET1不同,TET2表现出促进CKD进展的作用。Liu等[63]发现在UUO小鼠模型中TET2表达上调可促进纤维化,这与上调缺氧诱导因子-1α触发的代谢重塑有关。TET2上调可能通过α平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)启动子低甲基化,促进α-SMA表达和肾脏纤维化。此外,TET2在db/db糖尿病小鼠模型和高糖诱导的人肾小球系膜细胞中表达增加,TET2通过DNA去甲基化上调TGF-β1表达,促进DKD进展[64]。TET家族的另一个成员TET3可能在抑制UUO肾小管间质纤维化方面发挥作用。Tampe等[65]研究显示在UUO、DKD、肾毒性血清肾炎和5/6肾切除诱导的肾脏纤维化小鼠模型中,TET3表达下调可通过RASAL1启动子高甲基化,抑制RASAL1表达,同时,骨形态蛋白7可能通过上调TET3和促使RASAL1启动子甲基化水平正常,进而抑制纤维化。因此,TET可能会成为UUO抗肾小管间质纤维化的干预靶点。Xu等[66]基于成簇规律间隔短回文重复序列及其相关蛋白9的基因特异性双加氧酶质粒,采用慢病毒传递系统,将靶向间质细胞的RASAL1融合蛋白和靶向小管上皮细胞的Klotho融合蛋白的质粒分别转染UUO模型,结果显示,激活的特异性基因可以明显减轻肾脏纤维化。该研究证实,基因特异性去甲基化技术对UUO抗肾小管间质纤维化具有显著疗效。由于DNA甲基化与RNA甲基化具有共同的酶系统,加之甲基化具有重要的生理功能且与多种疾病密切相关,因此,精准的靶向干预是基因甲基化治疗的挑战。

3 m5C RNA甲基化临床转化诊断和治疗潜能

目前关于m5C RNA甲基化的临床研究较少,主要集中在患者肾脏活检或外周血标本的m5C RNA甲基化相关酶异常表达方面。AKI患者肾活检标本中TET2表达下降[51],CKD患者肾活检标本中YBX1表达升高[57],有望成为潜在的新型生物学标志物(表3)。动物体内实验研究发现,过表达TET2或肼苯哒嗪诱导TET3表达可缓解AKI进展[52];YBX1与肾脏纤维化密切相关,其作用与亚细胞定位有关,通过HSc025诱导YBX1核穿梭有可能成为缓解CKD纤维化的新型干预靶点[58](表4)。
表3 m5C RNA甲基化临床转化诊断潜能
疾病 患者样本 定位 酶 表达 参考文献
AKI 肾活检 全肾 TET2 下降 [51]
IgA肾病 肾活检 全肾 YBX1 升高 [57]
局灶节段性肾小球硬化 肾活检 肾小球 YBX1 升高 [57]
DKD 肾活检 肾小球、肾小管间质 YBX1 升高 [57]
表4 m5C RNA甲基化临床转化治疗潜能
动物模型 干预 方式 剂量及疗程 作用 参考文献
AKI 肼苯哒嗪诱导TET3表达 腹腔注射 5 mg/kg,隔日1次 缓解AKI向CKD进展 [52]
UUO YBX1敲减 缓解肾小管间质损伤及肾脏纤维化 [58]
UUO HSc025诱导YBX1核穿梭 腹腔注射 75 mg/kg,UUO术后1 h、1 d和3 d 缓解肾脏纤维化 [58]
UUO 基于CRISPR/ cas9的基因特异性双加氧酶 输尿管注射 108 TU/80 μL,UUO术中单次 缓解肾脏纤维化 [66]
DKD 过表达TET1 血糖、血尿素氮和血肌酐下降,缓解DKD进展 [61]
DKD PJ-34抑制TET2表达 口服 30 mg/kg,每日1次 缓解DKD进展 [64]

4 总结及展望

m5C RNA甲基化在非肿瘤性肾脏疾病中的研究仍处于起步阶段。m5C RNA甲基化相关酶在非肿瘤性肾脏疾病发病中发挥着重要作用,其具体致病机制还有待进一步研究。m5C RNA甲基化有望成为疾病早期诊断和延缓疾病进展的潜在诊断和治疗靶点。
利益冲突 所有作者声明无利益冲突
作者贡献声明 张晨:研究选题、设计、数据收集、起草和修改论文;赵自霞:收集文献;吴私:筛选分析文献、绘制图表;栾军军:筛选分析文献、绘制图表;周华:最后的审阅和定稿、对研究工作各方面的诚信问题负责

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