微小RNA参与多囊卵巢综合征胰岛素抵抗的研究进展

doi:10.12280/gjszjk.20240463

摘要/Abstract

摘要：

胰岛素抵抗（insulin resistance，IR）是多囊卵巢综合征（polycystic ovary syndrome，PCOS）普遍的临床表现之一，同时在PCOS的病理过程中也占据着至关重要的位置。PCOS和IR密切相关，互为病因，二者相互作用形成恶性循环。近年来，关于微小RNA（microRNA，miRNA）在PCOS代谢紊乱病因学方面的研究逐渐深入，miRNA的表达水平在一定程度上与PCOS-IR的发生密切相关。总结近年来关于miRNA参与PCOS-IR的病理过程和致病机制等方面的研究进展。

关键词: 多囊卵巢综合征, 微RNAs, 胰岛素抵抗, 磷酸肌醇3-激酶类, 原癌基因蛋白质c-akt, 胰岛素受体底物蛋白质类

Abstract:

Insulin resistance (IR) characterizes not only a universal clinical feature of polycystic ovary syndrome (PCOS), but also serves a significant role in its pathophysiology. PCOS and IR are closely related and mutually cause each other. The interaction between IR and PCOS creates a detrimental cycle. There was substantial progress in the study of microRNAs (miRNAs) roles in PCOS-linked metabolic disturbances. The degree of miRNAs expression is intrinsically associated with PCOS-IR. In this paper, we discuss the miRNAs-related etiopathogenesis of PCOS-IR.

Key words: Polycystic ovary syndrome, MicroRNAs, Insulin resistance, Phosphatidylinositol 3-kinases, Proto-oncogene proteins c-akt, Insulin receptor substrate proteins

贾声晓, 孙淼, 匡洪影, 徐博雅. 微小RNA参与多囊卵巢综合征胰岛素抵抗的研究进展[J]. 国际生殖健康/计划生育杂志, 2025, 44(1): 59-64.

JIA Sheng-xiao, SUN Miao, KUANG Hong-ying, XU Bo-ya. Advancements in Research on MicroRNAs Related to Insulin Resistance in Polycystic Ovary Syndrome[J]. Journal of International Reproductive Health/Family Planning, 2025, 44(1): 59-64.

参考文献 40

[1]	Froment P, Plotton I, Giulivi C, et al. At the crossroads of fertility and metabolism: the importance of AMPK-dependent signaling in female infertility associated with hyperandrogenism[J]. Hum Reprod, 2022, 37(6):1207-1228. doi: 10.1093/humrep/deac067.
[2]	Heidarzadehpilehrood R, Pirhoushiaran M, Binti Osman M, et al. Unveiling Key Biomarkers and Therapeutic Drugs in Polycystic Ovary Syndrome (PCOS) Through Pathway Enrichment Analysis and Hub Gene-miRNA Networks[J]. Iran J Pharm Res, 2023, 22(1):e139985. doi: 10.5812/ijpr-139985.
[3]	Agbu P, Carthew RW. MicroRNA-mediated regulation of glucose and lipid metabolism[J]. Nat Rev Mol Cell Biol, 2021, 22(6):425-438. doi: 10.1038/s41580-021-00354-w.
[4]	张珊, 陈欢欢, 张磊, 等. 多囊卵巢综合征相关microRNAs的研究进展[J]. 生殖医学杂志, 2022, 31(10):1455-1461. doi: 10.3969/j.issn.1004-3845.2022.10.024.
[5]	Sen A, Prizant H, Light A, et al. Androgens regulate ovarian follicular development by increasing follicle stimulating hormone receptor and microRNA-125b expression[J]. Proc Natl Acad Sci U S A, 2014, 111(8):3008-3013. doi: 10.1073/pnas.1318978111.
[6]	Tan W, Dai F, Yang D, et al. MiR-93-5p promotes granulosa cell apoptosis and ferroptosis by the NF-kB signaling pathway in polycystic ovary syndrome[J]. Front Immunol, 2022,13:967151. doi: 10.3389/fimmu.2022.967151.
[7]	Cao J, Huo P, Cui K, et al. Follicular fluid-derived exosomal miR-143-3p/miR-155-5p regulate follicular dysplasia by modulating glycolysis in granulosa cells in polycystic ovary syndrome[J]. Cell Commun Signal, 2022, 20(1):61. doi: 10.1186/s12964-022-00876-6. pmid: 35534864
[8]	徐若翔, 尹徳, 张玮, 等. MicroRNA参与多囊卵巢综合征代谢紊乱的研究进展[J]. 中国计划生育和妇产科, 2023, 15(1):25-29, 36. doi: 10.3969/j.issn.1674-4020.2023.01.07.
[9]	杜趁香, 王焱, 武海英. 过表达miR-141-3p通过靶向下调PTEN并激活PI3K/Akt信号通路促进卵巢癌A2780细胞的恶性生物学行为[J]. 中国肿瘤生物治疗杂志, 2019, 26(5):563-568. doi: 10.3872/j.issn.1007-385x.2019.05.013.
[10]	Chang KJ, Chen JH, Chen KH. The Pathophysiological Mechanism and Clinical Treatment of Polycystic Ovary Syndrome: A Molecular and Cellular Review of the Literature[J]. Int J Mol Sci, 2024, 25(16):9037. doi: 10.3390/ijms25169037.
[11]	Singh S, Pal N, Shubham S, et al. Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics[J]. J Clin Med, 2023, 12(4):1454. doi: 10.3390/jcm12041454.
[12]	闻鑫, 张杨, 张跃辉, 等. 微小RNA对生殖内分泌疾病调控的研究进展[J]. 国际生殖健康/计划生育杂志, 2020, 39(5):425-431. doi: 10.3969/j.issn.1674-1889.2020.05.018.
[13]	McAllister JM, Han AX, Modi BP, et al. miRNA Profiling Reveals miRNA-130b-3p Mediates DENND1A Variant 2 Expression and Androgen Biosynthesis[J]. Endocrinology, 2019, 160(8):1964-1981. doi: 10.1210/en.2019-00013. pmid: 31184707
[14]	中华医学会糖尿病学分会. 胰岛素抵抗相关临床问题专家共识(2022版)[J]. 中华糖尿病杂志, 2022, 14(12):1368-1379. doi: 10.3760/cma.j.cn115791-20220905-00446.
[15]	刘萍, 李玮, 谢宝国, 等. 多囊卵巢综合征患者血清microRNA-27a、microRNA-320的表达及其临床意义[J]. 中国现代医学杂志, 2021, 31(15):19-25. doi: 10.3969/j.issn.1005-8982.2021.15.004.
[16]	樊宗成, 林云钗, 陈鑫, 等. 长链非编码RNA在代谢综合征组分中的研究进展[J]. 中华高血压杂志, 2022, 30(6):517-530. doi: 10.16439/j.issn.1673-7245.2022.06.005.
[17]	Jo S, Xu G, Jing G, et al. Human Glucagon Expression Is under the Control of miR-320a[J]. Endocrinology, 2021, 162(3):bqaa238. doi: 10.1210/endocr/bqaa238.
[18]	Li X. MiR-375, a microRNA related to diabetes[J]. Gene, 2014, 533(1):1-4. doi: 10.1016/j.gene.2013.09.105. pmid: 24120394
[19]	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, 2022, 26(6):1817-1825. doi: 10.1111/jcmm.16231.
[20]	Poy MN, Hausser J, Trajkovski M, et al. miR-375 maintains normal pancreatic alpha- and beta-cell mass[J]. Proc Natl Acad Sci U S A, 2009, 106(14):5813-5818. doi: 10.1073/pnas.0810550106.
[21]	Pierantoni M, Grassilli S, Brugnoli F, et al. Insights into the development of insulin-producing cells: Precursors correlated involvement of microRNA panels[J]. Life Sci, 2024,350:122762. doi: 10.1016/j.lfs.2024.122762.
[22]	杨昱红, 冯婷, 黄飞翔. miR-155/miR-200b在多囊卵巢综合征中的表达及相关性分析[J]. 中国妇幼保健, 2020, 35(18):3484-3487. doi: 10.19829/j.zgfybj.issn.1001-4411.2020.18.050.
[23]	Karagiannopoulos A, Cowan E, Eliasson L. miRNAs in the Beta Cell-Friends or Foes?[J]. Endocrinology, 2023, 164(5):bqad040. doi: 10.1210/endocr/bqad040.
[24]	Guo YC, Cao HD, Lian XF, et al. Molecular mechanisms of noncoding RNA and epigenetic regulation in obesity with consequent diabetes mellitus development[J]. World J Diabetes, 2023, 14(11):1621-1631. doi: 10.4239/wjd.v14.i11.1621.
[25]	尹丽红, 焦琳, 陈裕, 等. 多囊卵巢综合征大鼠子宫内膜中PI3K/AKT通路相关蛋白表达异常与胰岛素抵抗的关系[J]. 中国实验动物学报, 2022, 30(6):777-783. doi: 10.3969/j.issn.1005-4847.2022.06.006.
[26]	Zhong X, Jin F, Huang C, et al. DNA methylation of AMHRⅡ and INSR gene is associated with the pathogenesis of Polycystic Ovary Syndrome (PCOS)[J]. Technol Health Care, 2021, 29(S1):11-25. doi: 10.3233/THC-218002.
[27]	Yang WM, Min KH, Lee W. MiR-1271 upregulated by saturated fatty acid palmitate provokes impaired insulin signaling by repressing INSR and IRS-1 expression in HepG2 cells[J]. Biochem Biophys Res Commun, 2016, 478(4):1786-1791. doi: 10.1016/j.bbrc.2016.09.029.
[28]	Berenji E, Valipour Motlagh A, Fathi M, et al. Discovering therapeutic possibilities for polycystic ovary syndrome by targeting XIST and its associated ceRNA network through the analysis of transcriptome data[J]. Sci Rep, 2024, 14(1):6180. doi: 10.1038/s41598-024-56524-1. pmid: 38486041
[29]	王景娜, 焦保权. 血清miR-222、miR-874-3p和miR-27a联合诊断多囊卵巢综合征的应用价值[J]. 中南医学科学杂志, 2023, 51(2):238-241. doi: 10.15972/j.cnki.43-1509/r.2023.02.020.
[30]	Li D, Song H, Shuo L, et al. Gonadal white adipose tissue-derived exosomal MiR-222 promotes obesity-associated insulin resistance[J]. Aging(Albany NY), 2020, 12(22):22719-22743. doi: 10.18632/aging.103891.
[31]	Tong C, Wu Y, Zhang L, et al. Insulin resistance, autophagy and apoptosis in patients with polycystic ovary syndrome: Association with PI3K signaling pathway[J]. Front Endocrinol(Lausanne), 2022,13:1091147. doi: 10.3389/fendo.2022.1091147.
[32]	Krentowska A, Ponikwicka-Tyszko D, Łebkowska A, et al. Serum expression levels of selected microRNAs and their association with glucose metabolism in young women with polycystic ovary syndrome[J]. Pol Arch Intern Med, 2024, 134(1):16637. doi: 10.20452/pamw.16637.
[33]	Wang M, Liu M, Sun J, et al. MicroRNA-27a-3p affects estradiol and androgen imbalance by targeting Creb1 in the granulosa cells in mouse polycytic ovary syndrome model[J]. Reprod Biol, 2017, 17(4):295-304. doi: 10.1016/j.repbio.2017.09.005. pmid: 29089199
[34]	郑志然, 张可心, 李哲豪, 等. bta-miR-27a-3p靶向INSR在围产期奶牛脂肪肝发病中的作用机制[C]// 中国畜牧兽医学会兽医外科学分会. 中国畜牧兽医学会兽医外科学分会第十届二次理事会暨第25次学术研讨会论文集, 2021:248. doi: 10.26914/c.cnkihy.2021.081039.
[35]	陈建军, 王悦, 王玉梅. 外周血来源外泌体中miR-21水平与2型糖尿病患者胰岛素抵抗的相关性[J]. 现代实用医学, 2021, 33(4):533-535,封4. doi: 10.3969/j.issn.1671-0800.2021.04.060.
[36]	张云珠, 王宇华, 张爱, 等. PCOS患者外周血miR-21与PI3K/AKT通路的关系及其临床意义[J]. 中国妇产科临床杂志, 2022, 23(1):63-66. doi: 10.13390/j.issn.1672-1861.2022.01.019.
[37]	Wu D, Yu HC, Cha HN, et al. PAK4 phosphorylates and inhibits AMPKα to control glucose uptake[J]. Nat Commun, 2024, 15(1):6858. doi: 10.1038/s41467-024-51240-w. pmid: 39127697
[38]	Herman R, Kravos NA, Jensterle M, et al. Metformin and Insulin Resistance: A Review of the Underlying Mechanisms behind Changes in GLUT4-Mediated Glucose Transport[J]. Int J Mol Sci, 2022, 23(3):1264. doi: 10.3390/ijms23031264.
[39]	Chen YH, Heneidi S, Lee JM, et al. miRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue of polycystic ovary syndrome patients and women with insulin resistance[J]. Diabetes, 2013, 62(7):2278-2286. doi: 10.2337/db12-0963.
[40]	Liu J, Zhao Y, Chen L, et al. Role of metformin in functional endometrial hyperplasia and polycystic ovary syndrome involves the regulation of MEG3/miR-223/GLUT4 and SNHG20/miR-4486/GLUT4 signaling[J]. Mol Med Rep, 2022, 26(1):218. doi: 10.3892/mmr.2022.12734.