Advancements of MiR-202 in Reproductive Modulation

doi:10.12280/gjszjk.20240080

Abstract

Abstract:

MicroRNAs (miRNAs) have emerged as key regulators of diverse biological processes, including cell proliferation, differentiation, apoptosis, and metabolism. They are also actively involved in the reproductive and developmental processes of organisms. Among the let-7 family, miR-202 stands out owing to its high conservation across different species, implying the potential shared functions and regulatory roles. Substantial evidence from numerous studies underscores the involvement of miR-202 in a wide range of pathophysiological processes. Notably, it exerts significant inhibitory effects on tumor cell proliferation, migration, and invasion. Moreover, miR-202 plays a critical role in modulating the differentiation of T cell and exhibits the implications in the regulation of neurodevelopment and neurodegenerative diseases. The increasing evidence have indicated that miR-202 plays a crucial role in gamete development and the regulation of reproductive physiology. In this article, we review the regulatory roles of miR-202 in key reproductive processes, namely spermatogenesis, follicle development, and reproductive endocrine regulation.

Key words: MicroRNAs, Spermatogenesis, Sex differentiation, Germ cells, miR-202, Reproductive modulation

LIANG Yue, DONG Jie, XIAO Xi-feng, WANG Xiao-hong. Advancements of MiR-202 in Reproductive Modulation[J]. Journal of International Reproductive Health/Family Planning, 2024, 43(3): 228-233.

Figures/Tables 1

References 47

[1]	Saliminejad K, Khorram Khorshid HR, Soleymani Fard S, et al. An overview of microRNAs: Biology, functions, therapeutics, and analysis methods[J]. J Cell Physiol, 2019, 234(5):5451-5465. doi: 10.1002/jcp.27486. pmid: 30471116
[2]	Shang R, Lee S, Senavirathne G, et al. microRNAs in action: biogenesis, function and regulation[J]. Nat Rev Genet, 2023, 24(12):816-833. doi: 10.1038/s41576-023-00611-y. pmid: 37380761
[3]	Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14[J]. Cell, 1993, 75(5):843-854. doi: 10.1016/0092-8674(93)90529-y. pmid: 8252621
[4]	Liu W, Chen J, Yang C, et al. Expression of microRNA let-7 in cleavage embryos modulates cell fate determination and formation of mouse blastocysts[J]. Biol Reprod, 2022, 107(6):1452-1463. doi: 10.1093/biolre/ioac181.
[5]	Wang Y, Zhao J, Chen S, et al. Let-7 as a Promising Target in Aging and Aging-Related Diseases: A Promise or a Pledge[J]. Biomolecules, 2022, 12(8):1070. doi: 10.3390/biom12081070.
[6]	Ahmed EA, Rajendran P, Scherthan H. The microRNA-202 as a Diagnostic Biomarker and a Potential Tumor Suppressor[J]. Int J Mol Sci, 2022, 23(11):5870. doi: 10.3390/ijms23115870.
[7]	Chen J, Yin J, Liu J, et al. MiR-202-3p functions as a tumor suppressor and reduces cell migration and invasion in papillary thyroid carcinoma[J]. Eur Rev Med Pharmacol Sci, 2019, 23(3):1145-1150. doi: 10.26355/eurrev_201902_17005.
[8]	Lin Y, Chen Z, Lin S, et al. MiR-202 inhibits the proliferation and invasion of colorectal cancer by targeting UHRF1[J]. Acta Biochim Biophys Sin(Shanghai), 2019, 51(6):598-606. doi: 10.1093/abbs/gmz042.
[9]	Yu HY, Pan SS. MiR-202-5p suppressed cell proliferation, migration and invasion in ovarian cancer via regulating HOXB2[J]. Eur Rev Med Pharmacol Sci, 2020, 24(5):2256-2263. doi:10.26355/eurrev_202003_20491.
[10]	Wang L, Liu X, Song X, et al. MiR-202-5p Promotes M2 Polarization in Allergic Rhinitis by Targeting MATN2[J]. Int Arch Allergy Immunol, 2019, 178(2):119-127. doi: 10.1159/000493803.
[11]	Wang L, Yang X, Li W, et al. MiR-202-5p/MATN2 are associated with regulatory T-cells differentiation and function in allergic rhinitis[J]. Hum Cell, 2019, 32(4):411-417. doi: 10.1007/s13577-019-00266-0. pmid: 31493245
[12]	Li B, Huang Z, Meng J, et al. MiR-202-5p attenuates neurological deficits and neuronal injury in MCAO model rats and OGD-induced injury in Neuro-2a cells by targeting eIF4E-mediated induction of autophagy and inhibition of Akt/GSK-3β pathway[J]. Mol Cell Probes, 2020, 51:101497. doi: 10.1016/j.mcp.2019.101497.
[13]	Li Y, Liu L, Ding X, et al. Interleukin-1β attenuates the proliferation and differentiation of oligodendrocyte precursor cells through regulation of the microRNA-202-3p/β-catenin/Gli1 axis[J]. Int J Mol Med, 2020, 46(3):1217-1224. doi: 10.3892/ijmm.2020.4648.
[14]	Li Y, Li Q, Zhang O, et al. miR-202-5p protects rat against myocardial ischemia reperfusion injury by downregulating the expression of Trpv2 to attenuate the Ca²⁺ overload in cardiomyocytes[J]. J Cell Biochem, 2019, 120(8):13680-13693. doi: 10.1002/jcb.28641.
[15]	Wu HY, Wu JL, Ni ZL. Overexpression of microRNA-202-3p protects against myocardial ischemia-reperfusion injury through activation of TGF-β1/Smads signaling pathway by targeting TRPM6[J]. Cell Cycle, 2019, 18(5):621-637. doi: 10.1080/15384101.2019.1580494.
[16]	Li L, Wu F, Xie Y, et al. MiR-202-3p Inhibits Foam Cell Formation and is Associated with Coronary Heart Disease Risk in a Chinese Population[J]. Int Heart J, 2020, 61(1):153-159. doi: 10.1536/ihj.19-033. pmid: 31956131
[17]	Chen J, Gao C, Luo M, et al. MicroRNA-202 safeguards meiotic progression by preventing premature SEPARASE-mediated REC8 cleavage[J]. EMBO Rep, 2022, 23(8):e54298. doi: 10.15252/embr.202154298.
[18]	Janati-Idrissi S, de Abreu MR, Guyomar C, et al. Looking for a needle in a haystack: de novo phenotypic target identification reveals Hippo pathway-mediated miR-202 regulation of egg production[J]. Nucleic Acids Res, 2024, 52(2):738-754. doi: 10.1093/nar/gkad1154. pmid: 38059397
[19]	Reza A, Choi YJ, Han SG, et al. Roles of microRNAs in mammalian reproduction: from the commitment of germ cells to peri-implantation embryos[J]. Biol Rev Camb Philos Soc, 2019, 94(2):415-438. doi: 10.1111/brv.12459. pmid: 30151880
[20]	Ge RS, Li X, Wang Y. Leydig Cell and Spermatogenesis[J]. Adv Exp Med Biol, 2021, 1288:111-129. doi: 10.1007/978-3-030-77779-1_6.
[21]	Klees C, Alexandri C, Demeestere I, et al. The Role of microRNA in Spermatogenesis: Is There a Place for Fertility Preservation Innovation?[J]. Int J Mol Sci, 2023, 25(1):460. doi: 10.3390/ijms25010460.
[22]	Thumfart KM, Mansuy IM. What are Sertoli cells? Historical, methodological, and functional aspects[J]. Andrology, 2023, 11(5):849-859. doi: 10.1111/andr.13386.
[23]	Peng YJ, Tang XT, Shu HS, et al. Sertoli cells are the source of stem cell factor for spermatogenesis[J]. Development, 2023, 150(6):dev200706. doi: 10.1242/dev.200706.
[24]	Mohammed BT, Donadeu FX. Localization and in silico-based functional analysis of miR-202 in bull testis[J]. Reprod Domest Anim, 2022, 57(9):1082-1087. doi: 10.1111/rda.14159.
[25]	Wang X, Liu X, Qu M, et al. Sertoli cell-only syndrome: advances, challenges, and perspectives in genetics and mechanisms[J]. Cell Mol Life Sci, 2023, 80(3):67. doi: 10.1007/s00018-023-04723-w. pmid: 36814036
[26]	Dabaja AA, Mielnik A, Robinson BD, et al. Possible germ cell-Sertoli cell interactions are critical for establishing appropriate expression levels for the Sertoli cell-specific MicroRNA, miR-202-5p, in human testis[J]. Basic Clin Androl, 2015, 25:2. doi: 10.1186/s12610-015-0018-z. pmid: 25780590
[27]	Yang C, Yao C, Tian R, et al. miR-202-3p Regulates Sertoli Cell Proliferation, Synthesis Function, and Apoptosis by Targeting LRP6 and Cyclin D1 of Wnt/β-Catenin Signaling[J]. Mol Ther Nucleic Acids, 2019, 14:1-19. doi: 10.1016/j.omtn.2018.10.012.
[28]	Chen J, Gao C, Lin X, et al. The microRNA miR-202 prevents precocious spermatogonial differentiation and meiotic initiation during mouse spermatogenesis[J]. Development, 2021, 148(24):dev199799. doi: 10.1242/dev.199799.
[29]	Bannister SC, Smith CA, Roeszler KN, et al. Manipulation of estrogen synthesis alters MIR202* expression in embryonic chicken gonads[J]. Biol Reprod, 2011, 85(1):22-30. doi: 10.1095/biolreprod.110.088476. pmid: 21389341
[30]	Wainwright EN, Jorgensen JS, Kim Y, et al. SOX9 regulates microRNA miR-202-5p/3p expression during mouse testis differentiation[J]. Biol Reprod, 2013, 89(2):34. doi: 10.1095/biolreprod.113.110155. pmid: 23843232
[31]	Zhang Y, Yan Z, Qin Q, et al. Transcriptome Landscape of Human Folliculogenesis Reveals Oocyte and Granulosa Cell Interactions[J]. Mol Cell, 2018, 72(6):1021-1034.e4. doi: 10.1016/j.molcel.2018.10.029. pmid: 30472193
[32]	Guo X, Zhu Y, Guo L, et al. BCAA insufficiency leads to premature ovarian insufficiency via ceramide-induced elevation of ROS[J]. EMBO Mol Med, 2023, 15(4):e17450. doi: 10.15252/emmm.202317450.
[33]	Saucedo-Cuevas L, Ivanova E, Herta AC, et al. Genome-wide assessment of DNA methylation alterations induced by superovulation, sexual immaturity and in vitro follicle growth in mouse blastocysts[J]. Clin Epigenetics, 2023, 15(1):9. doi: 10.1186/s13148-023-01421-z. pmid: 36647174
[34]	Armisen J, Gilchrist MJ, Wilczynska A, et al. Abundant and dynamically expressed miRNAs, piRNAs, and other small RNAs in the vertebrate Xenopus tropicalis[J]. Genome Res, 2009, 19(10):1766-1775. doi: 10.1101/gr.093054.109. pmid: 19628731
[35]	Donadeu FX, Schauer SN. Differential miRNA expression between equine ovulatory and anovulatory follicles[J]. Domest Anim Endocrinol, 2013, 45(3):122-125. doi: 10.1016/j.domaniend.2013.06.006.
[36]	Sontakke SD, Mohammed BT, McNeilly AS, et al. Characterization of microRNAs differentially expressed during bovine follicle development[J]. Reproduction, 2014, 148(3):271-283. doi: 10.1530/REP-14-0140.
[37]	Xie S, Batnasan E, Zhang Q, et al. MicroRNA Expression is Altered in Granulosa Cells of Ovarian Hyperresponders[J]. Reprod Sci, 2016, 23(8):1001-1010. doi: 10.1177/1933719115625849. pmid: 26763554
[38]	Machtinger R, Rodosthenous RS, Adir M, et al. Extracellular microRNAs in follicular fluid and their potential association with oocyte fertilization and embryo quality: an exploratory study[J]. J Assist Reprod Genet, 2017, 34(4):525-533. doi: 10.1007/s10815-017-0876-8.
[39]	Li S, Lin G, Fang W, et al. Identification and Comparison of microRNAs in the Gonad of the Yellowfin Seabream (Acanthopagrus Latus)[J]. Int J Mol Sci, 2020, 21(16):5690. doi: 10.3390/ijms21165690.
[40]	Xu Q, Zhang Y, Chen Y, et al. Identification and differential expression of microRNAs in ovaries of laying and Broody geese (Anser cygnoides) by Solexa sequencing[J]. PLoS One, 2014, 9(2):e87920. doi: 10.1371/journal.pone.0087920.
[41]	Lu T, Zou X, Liu G, et al. A Preliminary Study on the Characteristics of microRNAs in Ovarian Stroma and Follicles of Chuanzhong Black Goat during Estrus[J]. Genes(Basel), 2020, 11(9):970. doi: 10.3390/genes11090970.
[42]	Lan K, Shen C, Li J, et al. A novel indel within the bovine SEPT7 gene is associated with ovary length[J]. Anim Biotechnol, 2023, 34(1):8-14. doi: 10.1080/10495398.2021.1929272.
[43]	Zhou X, He Y, Quan H, et al. HDAC1-Mediated lncRNA Stimulatory Factor of Follicular Development to Inhibit the Apoptosis of Granulosa Cells and Regulate Sexual Maturity through miR-202-3p-COX1 Axis[J]. Cells, 2023, 12(23):2734. doi: 10.3390/cells12232734.
[44]	Donadeu FX, Sontakke SD, Ioannidis J. MicroRNA indicators of follicular steroidogenesis[J]. Reprod Fertil Dev, 2016 Feb 11. doi: 10.1071/RD15282. Epub ahead of print.
[45]	Ran M, Hu S, Ouyang Q, et al. miR-202-5p Inhibits Lipid Metabolism and Steroidogenesis of Goose Hierarchical Granulosa Cells by Targeting ACSL3[J]. Animals(Basel), 2023, 13(3):325. doi: 10.3390/ani13030325.
[46]	Skaftnesmo KO, Edvardsen RB, Furmanek T, et al. Integrative testis transcriptome analysis reveals differentially expressed miRNAs and their mRNA targets during early puberty in Atlantic salmon[J]. BMC Genomics, 2017, 18(1):801. doi: 10.1186/s12864-017-4205-5. pmid: 29047327
[47]	Dong J, Wang L, Xing Y, et al. Dynamic peripheral blood microRNA expression landscape during the peri-implantation stage in women with successful pregnancy achieved by single frozen-thawed blastocyst transfer[J]. Hum Reprod Open, 2023, 2023(4):hoad034. doi: 10.1093/hropen/hoad034.

物种	miRNA名称	碱基序列	碱基长度（bp）	miRBase Acession number*
人	hsa-miR-202-3p	AGAGGUAUAGGGCAUGGGAA	20	MIMAT0002811
	hsa-miR-202-5p	UUCCUAUGCAUAUACUUCUUUG	22	MIMAT0002810
小鼠	mmu-miR-202-3p	AGAGGUAUAGCGCAUGGGAAGA	22	MIMAT0000235
	mmu-miR-202-5p	UUCCUAUGCAUAUACUUCUUU	21	MIMAT0004546
牛	bta-miR-202	UUCCUAUGCAUAUACUUCUUU	21	MIMAT0009259
斑马鱼	dre-miR-202-3p	AGAGGCAUAGGGCAUGGGAAAA	22	MIMAT0001864
	dre-miR-202-5p	UUCCUAUGCAUAUACCUCUUUG	22	MIMAT0003406
红原鸡	gga-miR-202-3p	AGAGGCAUAGAGCAUGGGAAAA	22	MIMAT0003355
	gga-miR-202-5p	UUUCCUAUGCAUAUACUUCUUU	22	MIMAT0003354

物种	miRNA名称	碱基序列	碱基长度（bp）	miRBase Acession number*
人	hsa-miR-202-3p	AGAGGUAUAGGGCAUGGGAA	20	MIMAT0002811
	hsa-miR-202-5p	UUCCUAUGCAUAUACUUCUUUG	22	MIMAT0002810
小鼠	mmu-miR-202-3p	AGAGGUAUAGCGCAUGGGAAGA	22	MIMAT0000235
	mmu-miR-202-5p	UUCCUAUGCAUAUACUUCUUU	21	MIMAT0004546
牛	bta-miR-202	UUCCUAUGCAUAUACUUCUUU	21	MIMAT0009259
斑马鱼	dre-miR-202-3p	AGAGGCAUAGGGCAUGGGAAAA	22	MIMAT0001864
	dre-miR-202-5p	UUCCUAUGCAUAUACCUCUUUG	22	MIMAT0003406
红原鸡	gga-miR-202-3p	AGAGGCAUAGAGCAUGGGAAAA	22	MIMAT0003355
	gga-miR-202-5p	UUUCCUAUGCAUAUACUUCUUU	22	MIMAT0003354