环状RNA在多囊卵巢综合征发生发展中的作用

doi:10.12280/gjszjk.20210307

摘要/Abstract

摘要：

多囊卵巢综合征（PCOS）是育龄期女性最常见的生殖内分泌疾病,发病率逐年增高。PCOS的临床表现具有高度异质性,且导致患者生活质量不同程度地下降。越来越多的证据表明,PCOS可能是一种复杂的多基因疾病,受到表观遗传和环境等多种因素的影响。一些研究对PCOS患者的卵巢组织、胎盘组织进行高通量测序或基因芯片分析,发现多种环状RNA（circRNA）存在差异表达,如hsa_circ_0006877、hsa_circ_ 0118530。这些差异表达的circRNA可能通过参与卵巢颗粒细胞增殖和凋亡、雄激素的合成和释放等影响卵母细胞的发育以及生殖内分泌平衡。综述circRNA在PCOS发生发展中的作用,为PCOS的临床治疗提供新思路。

关键词: 多囊卵巢综合征, 雄激素类, 细胞凋亡, 粒层细胞, 卵泡, 环状RNA, 卵泡发育

Abstract:

Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine diseases in women of childbearing age, and the incidence of PCOS increased year by year. The clinical manifestations of PCOS are highly heterogeneous, leading to different degrees of decline in the life quality of patients. There is growing evidence that PCOS may be a complex polygenetic disease with strong epigenetic and environmental influences. Some studies conducted high-throughput sequencing or gene chip analysis on ovarian tissues and placental tissues of PCOS patients found multiple differentially expressed circRNA, such as hsa_circ_0006877, hsa_circ_0118530. These differentially expressed circRNA may affect oocyte development and reproductive endocrine balance through their involvement in the ovarian granulosa cell proliferation and apoptosis, androgen synthesis and release. This article reviews the role of circRNA in the occurrence and development of PCOS.

Key words: Polycystic ovary syndrome, Androgens, Apoptosis, Granulosa cells, Ovarian follicle, Circular RNA, Follicle development

皇灵俐, 冯睿芝, 钱云. 环状RNA在多囊卵巢综合征发生发展中的作用[J]. 国际生殖健康/计划生育, 2021, 40(6): 509-513.

HUANG Ling-li, FENG Rui-zhi, QIAN Yun. Circular RNA in Pathophysiology of Polycystic Ovary Syndrome[J]. Journal of International Reproductive Health/Family Planning, 2021, 40(6): 509-513.

图/表 1

参考文献 28

[1]	Ye W, Xie T, Song Y, et al. The role of androgen and its related signals in PCOS[J]. J Cell Mol Med, 2021, 25(4):1825-1837. doi: 10.1111/jcmm.16205. doi: 10.1111/jcmm.16205 URL
[2]	Khan MJ, Ullah A, Basit S. Genetic Basis of Polycystic Ovary Syndrome (PCOS): Current Perspectives[J]. Appl Clin Genet, 2019, 12:249-260. doi: 10.2147/TACG.S200341. doi: 10.2147/TACG.S200341 URL
[3]	Kristensen LS, Andersen MS, Stagsted L, et al. The biogenesis, biology and characterization of circular RNAs[J]. Nat Rev Genet, 2019, 20(11):675-691. doi: 10.1038/s41576-019-0158-7. doi: 10.1038/s41576-019-0158-7 pmid: 31395983
[4]	Ma Z, Zhao H, Zhang Y, et al. Novel circular RNA expression in the cumulus cells of patients with polycystic ovary syndrome[J]. Arch Gynecol Obstet, 2019, 299(6):1715-1725. doi: 10.1007/s00404-019-05122-y. doi: 10.1007/s00404-019-05122-y URL
[5]	Zhao C, Zhou Y, Shen X, et al. Circular RNA expression profiling in the fetal side of placenta from maternal polycystic ovary syndrome and circ_0023942 inhibits the proliferation of human ovarian granulosa cell[J]. Arch Gynecol Obstet, 2020, 301(4):963-971. doi: 10.1007/s00404-020-05495-5. doi: 10.1007/s00404-020-05495-5 URL
[6]	Jia C, Wang S, Yin C, et al. Loss of hsa_circ_0118530 inhibits human granulosa-like tumor cell line KGN cell injury by sponging miR-136[J]. Gene, 2020, 744:144591. doi: 10.1016/j.gene.2020.144591. doi: 10.1016/j.gene.2020.144591 URL
[7]	Wu G, Xia J, Yang Z, et al. CircASPH promotes KGN cells proliferation through miR-375/MAP2K6 axis in Polycystic Ovary Syndrome[J]. J Cell Mol Med, 2020 Dec 28. doi: 10.1111/jcmm.16231. doi: 10.1111/jcmm.16231
[8]	Zhou WY, Cai ZR, Liu J, et al. Circular RNA: metabolism, functions and interactions with proteins[J]. Mol Cancer, 2020, 19(1):172. doi: 10.1186/s12943-020-01286-3. doi: 10.1186/s12943-020-01286-3 URL
[9]	Zaphiropoulos PG. Circular RNAs from transcripts of the rat cytochrome P450 2C24 gene: correlation with exon skipping[J]. Proc Natl Acad Sci U S A, 1996, 93(13):6536-6541. doi: 10.1073/pnas.93.13.6536. doi: 10.1073/pnas.93.13.6536 pmid: 8692851
[10]	Jeck WR, Sorrentino JA, Wang K, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats[J]. RNA, 2013, 19(2):141-157. doi: 10.1261/rna.035667.112. doi: 10.1261/rna.035667.112 URL
[11]	Salzman J, Gawad C, Wang PL, et al. Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types[J]. PLoS One, 2012, 7(2):e30733. doi: 10.1371/journal.pone.0030733. doi: 10.1371/journal.pone.0030733 URL
[12]	Wang L, Long H, Zheng Q, et al. Circular RNA circRHOT1 promotes hepatocellular carcinoma progression by initiation of NR2F6 expression[J]. Mol Cancer, 2019, 18(1):119. doi: 10.1186/s12943-019-1046-7. doi: 10.1186/s12943-019-1046-7 URL
[13]	Li Z, Huang C, Bao C, et al. Exon-intron circular RNAs regulate transcription in the nucleus[J]. Nat Struct Mol Biol, 2015, 22(3):256-264. doi: 10.1038/nsmb.2959. doi: 10.1038/nsmb.2959 URL
[14]	Wang Y, Liu J, Ma J, et al. Exosomal circRNAs: biogenesis, effect and application in human diseases[J]. Mol Cancer, 2019, 18(1):116. doi: 10.1186/s12943-019-1041-z. doi: 10.1186/s12943-019-1041-z URL
[15]	Yan Y, Fu G, Ye Y, et al. Exosomes participate in the carcinogenesis and the malignant behavior of gastric cancer[J]. Scand J Gastroenterol, 2017, 52(5):499-504. doi: 10.1080/00365521.2016.1278458. doi: 10.1080/00365521.2016.1278458 URL
[16]	Li X, Yang L, Chen LL. The Biogenesis, Functions, and Challenges of Circular RNAs[J]. Mol Cell, 2018, 71(3):428-442. doi: 10.1016/j.molcel.2018.06.034. doi: 10.1016/j.molcel.2018.06.034 URL
[17]	Rybak-Wolf A, Stottmeister C, Glažar P, et al. Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed[J]. Mol Cell, 2015, 58(5):870-885. doi: 10.1016/j.molcel.2015.03.027. doi: 10.1016/j.molcel.2015.03.027 pmid: 25921068
[18]	Conn SJ, Pillman KA, Toubia J, et al. The RNA binding protein quaking regulates formation of circRNAs[J]. Cell, 2015, 160(6):1125-1134. doi: 10.1016/j.cell.2015.02.014. doi: 10.1016/j.cell.2015.02.014 URL
[19]	Wang LP, Peng XY, Lv XQ, et al. High throughput circRNAs sequencing profile of follicle fluid exosomes of polycystic ovary syndrome patients[J]. J Cell Physiol, 2019 Feb 18. doi: 10.1002/jcp.28201. doi: 10.1002/jcp.28201
[20]	Huang X, Wu B, Chen M, et al. Depletion of exosomal circLDLR in follicle fluid derepresses miR-1294 function and inhibits estradiol production via CYP19A1 in polycystic ovary syndrome[J]. Aging (Albany NY), 2020, 12(15):15414-15435. doi: 10.18632/aging.103602. doi: 10.18632/aging.103602
[21]	Che Q, Liu M, Xu J, et al. Characterization of circular RNA expression profiles in cumulus cells from patients with polycystic ovary syndrome[J]. Fertil Steril, 2019, 111(6):1243-1251.e1. doi: 10.1016/j.fertnstert.2019.02.023. doi: S0015-0282(19)30134-7 pmid: 30979425
[22]	Zhang C, Liu J, Lai M, et al. Circular RNA expression profiling of granulosa cells in women of reproductive age with polycystic ovary syndrome[J]. Arch Gynecol Obstet, 2019, 300(2):431-440. doi: 10.1007/s00404-019-05129-5. doi: 10.1007/s00404-019-05129-5 URL
[23]	Blesson CS, Chinnathambi V, Hankins GD, et al. Prenatal testosterone exposure induces hypertension in adult females via androgen receptor-dependent protein kinase Cδ-mediated mechanism[J]. Hypertension, 2015, 65(3):683-690. doi: 10.1161/HYPERTENSIONAHA.114.04521. doi: 10.1161/HYPERTENSIONAHA.114.04521
[24]	Agarwal SK, Judd HL, Magoffin DA. A mechanism for the suppression of estrogen production in polycystic ovary syndrome[J]. J Clin Endocrinol Metab, 1996, 81(10):3686-3691. doi: 10.1210/jcem.81.10.8855823. doi: 10.1210/jcem.81.10.8855823
[25]	Chen J, Shen S, Tan Y, et al. The correlation of aromatase activity and obesity in women with or without polycystic ovary syndrome[J]. J Ovarian Res, 2015, 8:11. doi: 10.1186/s13048-015-0139-1. doi: 10.1186/s13048-015-0139-1 pmid: 25881575
[26]	Wang J, Chu K, Wang Y, et al. Procr-expressing granulosa cells are highly proliferative and are important for follicle development[J]. iScience, 2021, 24(2):102065. doi: 10.1016/j.isci.2021.102065. doi: 10.1016/j.isci.2021.102065 URL
[27]	Xu L, Ma Y, Zhang H, et al. HMGA2 regulates circular RNA ASPH to promote tumor growth in lung adenocarcinoma[J]. Cell Death Dis, 2020, 11(7):593. doi: 10.1038/s41419-020-2726-3. doi: 10.1038/s41419-020-2726-3 URL
[28]	Deng L, Chen Q, Xie J, et al. circPUM1 promotes polycystic ovary syndrome progression by sponging to miR-760[J]. Gene, 2020, 754:144903. doi: 10.1016/j.gene.2020.144903. doi: 10.1016/j.gene.2020.144903 URL