实用医学杂志 ›› 2024, Vol. 40 ›› Issue (16): 2352-2356.doi: 10.3969/j.issn.1006-5725.2024.16.024
• 综述 • 上一篇
收稿日期:
2024-01-08
出版日期:
2024-08-25
发布日期:
2024-08-26
通讯作者:
刘洋
E-mail:13518735544@163.com
基金资助:
Received:
2024-01-08
Online:
2024-08-25
Published:
2024-08-26
Contact:
Yang. LIU
E-mail:13518735544@163.com
摘要:
N6-甲基腺嘌呤(m6A)修饰参与多种生物学过程,动态调控RNA的稳定性。当m6A修饰发生改变时,影响卵泡发育、颗粒细胞增殖及卵母细胞发育等过程,参与良性卵巢相关疾病的发生发展,如多囊卵巢综合征(PCOS)、早发性卵巢功能不全(POI)、子宫内膜异位症(EMS)等,导致女性生育力下降。因此,本文对m6A修饰在良性卵巢相关疾病中的作用和研究进展进行综述,旨在为后续开展改善生育力的研究提供新的思路。
中图分类号:
吴妍芝,刘洋. m6A修饰在良性卵巢相关疾病的研究进展[J]. 实用医学杂志, 2024, 40(16): 2352-2356.
Yanzhi WU,Yang. LIU. Research progress of m6A modification in benign ovarian related diseases[J]. The Journal of Practical Medicine, 2024, 40(16): 2352-2356.
表1
m6A修饰相关检测技术"
检测技术 | 优点 | 缺点 | |
---|---|---|---|
定量检测技术 | 比色法[ | 操作简单,方便快捷,灵敏度高 | 无特异性 |
斑点印迹法[ | 时间周期短,成本低 | 半定量形式 | |
HPLC-MS/MS[ | 精准,敏感度和特异度高,样本量大 | 样品前处理繁琐,分析时间长 | |
SCAELET[ | - | 步骤复杂、实验周期长 使用放射性试剂 | |
定位检测技术 | MeB-RIP-seq[ | 样品起始量低,全转录组信息覆盖 | 重复性低,分辨率低 |
mi CllP-seq[ | - | 依赖抗体,灵敏性和重复性、准确性相对较差 | |
定量定位检测技术 | m6A-SAC-seq[ | 检测样本多样,重复性好,精度高,样本量要求低 | - |
m6A-REF-seq[ | 不依赖抗体,精准检测 | 不能覆盖所有位点 |
表2
m6A修饰与良性卵巢相关疾病的相关性"
机制 | ||
---|---|---|
PCOS | 甲基化酶METTL3 | 缺陷METTL3,可能导致细胞凋亡[ |
去甲基化酶FTO | FTO表达上调,导致GCs障碍[ | |
阅读蛋白YTHDF1 | YTHDF1表达降低,改善PCOS症状[ | |
POI | 甲基化酶METTL3 | METTL3表达上调,导致POF[ |
阅读蛋白YTHDF2 | 致病变异与POI发生有关[ | |
甲基化酶KIAA1429 | 颗粒细胞凋亡,可能造成卵泡闭锁[ | |
去甲基化酶ALKBH5和FTO | 表达下调,导致POF[ | |
EMS | 甲基化酶METTL3 | 表达上调,抑制ESCs的增殖[ |
甲基化酶METTL14 | 表达下调,促进ESCs增殖和入侵[ | |
阅读蛋白YTHDF2 | 促进ESC的细胞衰老[ | |
去甲基化酶FTO | 上调FTO,促进子ESCs增殖[ |
1 |
SENDINC E, SHI Y. RNA m6A methylation across the transcriptome[J]. Mol Cell, 2023, 83(3): 428-441. doi:10.1016/j.molcel.2023.01.006
doi: 10.1016/j.molcel.2023.01.006 |
2 |
HUANG E, CHEN L. RNA N6-methyladenosine modification in female reproductive biology and pathophysiology[J]. Cell Commun Signal, 2023, 21(1): 53. doi:10.1186/s12964-023-01078-4
doi: 10.1186/s12964-023-01078-4 |
3 |
SUN X, ZHANG Y, HU Y, et al. Decreased expression of m6A demethylase FTO in ovarian aging[J]. Arch Gynecol Obstet, 2021, 303(5): 1363-1369. doi:10.1007/s00404-020-05895-7
doi: 10.1007/s00404-020-05895-7 |
4 | 王焓,段萍. 脂肪和肥胖相关基因通过TLR2/p38信号通路促进异位子宫内膜间质细胞纤维化[J]. 温州医科大学学报, 2022,52(3): 180-185+193. |
5 |
JING Y X, LI H X, YUE F, et al. N6-methyladenosine demethylase FTO related to hyperandrogenism in PCOS via AKT pathway[J]. Gynecol Endocrinol, 2023, 39(1): 2276167. doi:10.1080/09513590.2023.2276167
doi: 10.1080/09513590.2023.2276167 |
6 | 唐立丽,王昕宇,张杰,等. m6A甲基化修饰在急性肾损伤中的研究进展[J]. 实用医学杂志, 2024,40(2): 278-282. |
7 | 钱晓芬,曾平,刘金富,等. m6A RNA甲基化修饰相关酶的研究进展[J]. 中国免疫学杂志, 2023,39(5): 1073-1084. |
8 | 邹菊红,黄艳娜,蒋钦杨. RNA N6-腺苷酸甲基化修饰及其生物学功能[J]. 中国畜牧兽医, 2021,48(4): 1196-1203. |
9 |
JIANG X, LIU B, NIE Z, et al. The role of m6A modification in the biological functions and diseases[J]. Signal Transduct Target Ther, 2021, 6(1): 74. doi:10.1038/s41392-020-00450-x
doi: 10.1038/s41392-020-00450-x |
10 |
SHEN D, WANG B, GAO Y, et al. Detailed resume of RNA m6A demethylases[J]. Acta Pharmaceut Sin B, 2022, 12(5): 2193-2205. doi:10.1016/j.apsb.2022.01.003
doi: 10.1016/j.apsb.2022.01.003 |
11 |
彭佳欣,张自辉,洪莉. m6A修饰在卵巢癌中的研究进展[J]. 实用医学杂志, 2023,39(12): 1577-1583. doi:10.3969/j.issn.1006-5725.2023.12.020
doi: 10.3969/j.issn.1006-5725.2023.12.020 |
12 |
ZACCARA S, RIES R J, JAFFREY S R. Reading, writing and erasing mRNA methylation[J]. Nature Rev Mol Cell Biol, 2019, 20(10): 608-624. doi:10.1038/s41580-019-0168-5
doi: 10.1038/s41580-019-0168-5 |
13 |
BOULIAS K, GREER E L. Biological roles of adenine methylation in RNA[J]. Nature Rev Gen, 2023, 24(3): 143-160. doi:10.1038/s41576-022-00534-0
doi: 10.1038/s41576-022-00534-0 |
14 |
DENG K, NING X, REN X, et al. Transcriptome-wide N6-methyladenosine methylation landscape of coronary artery disease[J]. Epigenomics, 2021, 13(10): 793-808. doi:10.2217/epi-2020-0372
doi: 10.2217/epi-2020-0372 |
15 |
ZHAO S, ZHANG B, YUAN H, et al. IGF2BP2 promotes the progression of ovarian endometriosis by regulating m6A-modified MEIS2 and GATA6[J]. Int J Biochem Cell Biol, 2022, 152: 106296. doi:10.1016/j.biocel.2022.106296
doi: 10.1016/j.biocel.2022.106296 |
16 |
YANG K, SUN J, ZHANG Z, et al. Reduction of mRNA m6A associates with glucose metabolism via YTHDC1 in human and mice[J]. Diab Res Clin Pract, 2023, 198: 110607. doi:10.1016/j.diabres.2023.110607
doi: 10.1016/j.diabres.2023.110607 |
17 |
LIU N, PARISIEN M, DAI Q, et al. Probing N6-methyladenosine RNA modification status at single nucleotide resolution in mRNA and long noncoding RNA[J]. RNA, 2013, 19(12): 1848-1856. doi:10.1261/rna.041178.113
doi: 10.1261/rna.041178.113 |
18 |
XUE A, HUANG Y, LI M, et al. Comprehensive Analysis of Differential m6A RNA Methylomes in the Hippocampus of Cocaine-Conditioned Mice[J]. Mol Neurobiol, 2021, 58(8): 3759-3768. doi:10.1007/s12035-021-02363-4
doi: 10.1007/s12035-021-02363-4 |
19 |
LINDER B, GROZHIK A V, OLARERIN-GEORGE A O, et al. Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome[J]. Nat Methods, 2015, 12(8): 767-772. doi:10.1038/nmeth.3453
doi: 10.1038/nmeth.3453 |
20 |
ZHANG Z, CHEN L Q, ZHAO Y L, et al. Single-base mapping of m6A by an antibody-independent method[J]. Sci Adv, 2019, 5(7): eaax0250. doi:10.1126/sciadv.aax0250
doi: 10.1126/sciadv.aax0250 |
21 |
HU L, LIU S, PENG Y, et al. m6A RNA modifications are measured at single-base resolution across the mammalian transcriptome[J]. Nat Biotechnol, 2022, 40(8): 1210-1219. doi:10.1038/s41587-022-01243-z
doi: 10.1038/s41587-022-01243-z |
22 |
CARSON S A, KALLEN A N. Diagnosis and Management of Infertility: A Review[J]. JAMA, 2021, 326(1): 65. doi:10.1001/jama.2021.4788
doi: 10.1001/jama.2021.4788 |
23 |
GENG X, ZHAO J, HUANG J, et al. lnc-MAP3K13-7:1 Inhibits Ovarian GC Proliferation in PCOS via DNMT1 Downregulation-Mediated CDKN1A Promoter Hypomethylation[J]. Mol Ther, 2021, 29(3): 1279-1293. doi:10.1016/j.ymthe.2020.11.018
doi: 10.1016/j.ymthe.2020.11.018 |
24 |
MU H, ZHANG T, YANG Y, et al. METTL3-mediated mRNA N6-methyladenosine is required for oocyte and follicle development in mice[J]. Cell Death Dis, 2021, 12(11): 989. doi:10.1038/s41419-021-04272-9
doi: 10.1038/s41419-021-04272-9 |
25 |
ZHANG S, DENG W, LIU Q, et al. Altered m6 A modification is involved in up-regulated expression of FOXO3 in luteinized granulosa cells of non-obese polycystic ovary syndrome patients[J]. J Cell Mol Med, 2020, 24(20): 11874-11882. doi:10.1111/jcmm.15807
doi: 10.1111/jcmm.15807 |
26 |
ZHOU L, HAN X, LI W, et al. N6-methyladenosine Demethylase FTO Induces the Dysfunctions of Ovarian Granulosa Cells by Upregulating Flotillin 2[J]. Reprod Sci, 2022, 29(4): 1305-1315. doi:10.1007/s43032-021-00664-6
doi: 10.1007/s43032-021-00664-6 |
27 |
ZHANG Y, ZHOU H, DING C. The ameliorative effect of CangFu Daotan Decoction on polycystic ovary syndrome of rodent model is associated with m6A methylation and Wnt/β-catenin pathway[J]. Gynecol Endocrinol, 2023, 39(1): 2181637. doi:10.1080/09513590.2023.2181637
doi: 10.1080/09513590.2023.2181637 |
28 | 陈蓉,罗敏. 早发性卵巢功能不全的相关术语[J]. 中国实用妇科与产科杂志, 2023,39(9): 869-871. |
29 |
ZHANG J, YAN L, WANG Y, et al. In vivo and in vitro activation of dormant primordial follicles by EGF treatment in mouse and human[J]. Clin Translat Med, 2020, 10(5): e182. doi:10.1002/ctm2.182
doi: 10.1002/ctm2.182 |
30 |
HUANG B, DING C, ZOU Q, et al. Cyclophosphamide Regulates N6-Methyladenosine and m6A RNA Enzyme Levels in Human Granulosa Cells and in Ovaries of a Premature Ovarian Aging Mouse Model[J]. Front Endocrinol, 2019, 10: 415. doi:10.3389/fendo.2019.00415
doi: 10.3389/fendo.2019.00415 |
31 |
McGLACKEN-BYRNE S M, DEL VALLE I, QUESNE STABEJ P L, et al. Pathogenic variants in the human m6A reader YTHDC2 are associated with primary ovarian insufficiency[J]. JCI Insight, 2022, 7(5): e154671. doi:10.1172/jci.insight.154671
doi: 10.1172/jci.insight.154671 |
32 |
HU Y, OUYANG Z, SUI X, et al. Oocyte competence is maintained by m6A methyltransferase KIAA1429-mediated RNA metabolism during mouse follicular development[J]. Cell Death Differ, 2020, 27(8): 2468-2483. doi:10.1038/s41418-020-0516-1
doi: 10.1038/s41418-020-0516-1 |
33 |
LI Y, LI M, LIU J, et al. Altered m6A modification is involved YAP-mediated apoptosis response in 4-vinylcyclohexene diepoxide induced ovotoxicity[J]. Ecotoxicol Environm Safety, 2023, 262: 115192. doi:10.1016/j.ecoenv.2023.115192
doi: 10.1016/j.ecoenv.2023.115192 |
34 |
ZHAO Y, SHI Y, SHEN H, et al. m6A-binding proteins: the emerging crucial performers in epigenetics[J]. J Hematol Oncol, 2020, 13(1): 35. doi:10.1186/s13045-020-00872-8
doi: 10.1186/s13045-020-00872-8 |
35 |
BECKER C M, BOKOR A, HEIKINHEIMO O, et al. ESHRE guideline: endometriosis[J]. Human Reprod Open, 2022, 2022(2): hoac009. doi:10.1093/hropen/hoac009
doi: 10.1093/hropen/hoac009 |
36 | 冷金花,李晓燕. 子宫内膜异位症诊治中有争议的几个问题[J]. 中国实用妇科与产科杂志, 2021,37(3): 273-276. |
37 |
WARZECHA D, SZYMUSIK I, WIELGOS M, et al. The Impact of Endometriosis on the Quality of Life and the Incidence of Depression-A Cohort Study[J]. Int J Environm Res Public Health, 2020, 17(10): 3641. doi:10.3390/ijerph17103641
doi: 10.3390/ijerph17103641 |
38 |
MATHIYALAGAN P, ADAMIAK M, MAYOURIAN J, et al. FTO-Dependent N6-Methyladenosine Regulates Cardiac Function During Remodeling and Repair[J]. Circulation, 2019, 139(4): 518-532. doi:10.1161/circulationaha.118.033794
doi: 10.1161/circulationaha.118.033794 |
39 |
LI T, ZHUANG Y, YANG W, et al. Silencing of METTL3 attenuates cardiac fibrosis induced by myocardial infarction via inhibiting the activation of cardiac fibroblasts[J]. FASEB J, 2021, 35(2):e21162. doi:10.1096/fj.201903169r
doi: 10.1096/fj.201903169r |
40 |
LI X, XIONG W, LONG X, et al. Inhibition of METTL3/m6A/miR126 promotes the migration and invasion of endometrial stromal cells in endometriosis[J]. Biol Reproduct, 2021, 105(5): 1221-1233. doi:10.1093/biolre/ioab152
doi: 10.1093/biolre/ioab152 |
41 |
ZHANG Q. METTL3 is aberrantly expressed in endometriosis and suppresses proliferation, invasion, and migration of endometrial stromal cells[J]. Kaohsiung J Med Sci, 2023, 39(3): 266-277. doi:10.1002/kjm2.12626
doi: 10.1002/kjm2.12626 |
42 |
WANG X, WANG J, ZHAO X, et al. METTL3-mediated m6A modification of SIRT1 mRNA inhibits progression of endometriosis by cellular senescence enhancing[J]. J Translat Med, 2023, 21(1): 407. doi:10.1186/s12967-023-04209-0
doi: 10.1186/s12967-023-04209-0 |
43 |
SHEN L, ZHANG C, ZHANG Y, et al. METTL3 and METTL14-mediated N6-methyladenosine modification promotes cell proliferation and invasion in a model of endometriosis[J]. Reprod Biomed Online, 2023, 46(2): 255-265. doi:10.1016/j.rbmo.2022.10.010
doi: 10.1016/j.rbmo.2022.10.010 |
44 |
WANG H, LIANG Z, GOU Y, et al. FTO-dependent N(6)-Methyladenosine regulates the progression of endometriosis via the ATG5/PKM2 Axis[J]. Cell Signal, 2022, 98: 110406. doi:10.1016/j.cellsig.2022.110406
doi: 10.1016/j.cellsig.2022.110406 |
[1] | 李文昕,卢敏君,林莉,刘月琴,朱小兰. circRAF1调节人卵巢颗粒细胞的增殖与凋亡[J]. 实用医学杂志, 2024, 40(7): 910-917. |
[2] | 黄平,兰康云,梁炎春,陈勍,金瑛,陈光元,牛刚. 深部浸润型子宫内膜异位症病灶微生物组学研究[J]. 实用医学杂志, 2024, 40(21): 3023-3030. |
[3] | 孙六娜 卢如玲 张淑婷 李安 蓝红云 何艳霞 江湧 . 寿胎丸对肾虚型多囊卵巢综合征不孕患者子宫内膜容受性及相关因子的影响 [J]. 实用医学杂志, 2023, 39(3): 355-359. |
[4] | 吴玉良 吴春玲 吴丹 . 血清sFLT1、CTRP3水平与子宫内膜异位症的相关性 [J]. 实用医学杂志, 2023, 39(14): 1798-1803. |
[5] | 张莹 刘恩 . 提高非经典21羟化酶缺乏症临床诊治水平: 局限与展望 [J]. 实用医学杂志, 2023, 39(1): 1-5. |
[6] | . 反复种植失败的子宫内膜异位症患者冻融胚胎移植结局的影响因素 [J]. 实用医学杂志, 2022, 38(9): 1070-1075. |
[7] | 杨如玉 梁炎春 韦雅婧 黄碧淇 杨帆 谭灏 温磊 陆曦 牛刚. 缺氧诱导HIF⁃1α在子宫内膜异位症巨噬细胞极化异常的作用及机制研究 [J]. 实用医学杂志, 2022, 38(8): 964-969. |
[8] | 马颖 黄思霞 黄柳菁 蔡朝霞 马菘 梁晓珊 . 微生物组学——子宫内膜异位症病因学研究新方向 [J]. 实用医学杂志, 2022, 38(24): 3027-3031. |
[9] | 陈璐 林莉 朱小兰, . 巨噬细胞极化在子宫内膜异位症中的研究进展[J]. 实用医学杂志, 2022, 38(21): 2751-2754. |
[10] | 熊翔鹏 夏雷震 艾小燕 . 血栓弹力图在子宫内膜异位症中的应用价值 [J]. 实用医学杂志, 2022, 38(17): 2226-2230. |
[11] | 李荔 周嘉禾 李末娟 钟明琳 张小伟 许秋仪 梁莲云. 多囊卵巢综合征表观遗传学、代谢组学、肠道菌群新机制前沿展望 [J]. 实用医学杂志, 2022, 38(16): 1987-1992. |
[12] | 孙璐 范晓东 李雯 杨潇潇 朱颖军. 青春期子宫内膜异位症89例 [J]. 实用医学杂志, 2022, 38(14): 1778-1781. |
[13] | 韦雅婧, 梁炎春, 杨如玉, 雷舜天, 王泽海, 牛刚. 健康女性与子宫内膜异位症患者肠道菌群微生物组学研究 [J]. 实用医学杂志, 2021, 37(10): 1279-1283. |
[14] | 许明桃 郑玮琳 梁雪芳 曹立幸 陈韵婷 . 益气消癥方配合周期疗法治疗子宫内膜异位症痛经的临床观察 [J]. 实用医学杂志, 2021, 37(10): 1357-1360. |
[15] | 谭秋晓, 张红梅, 李洁明, 陈志静, 张小伟, 李荔. 多囊卵巢综合征患者抑郁和焦虑发病现状及影响因素分析[J]. 实用医学杂志, 2020, 36(23): 3288-3292. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||