miRNA和lncRNA调控反刍动物卵泡发育的分子机制研究进展

doi:10.16431/j.cnki.1671-7236.2025.02.027

摘要/Abstract

摘要： 卵泡发育是决定排卵率和产羔数的重要因素，直接影响母畜生殖机能和繁殖力高低。随着近年来组学技术的发展，微小RNA(microRNA，miRNA)和长链非编码RNA(long non-coding RNA，lncRNA)在反刍动物的卵泡动态发育过程中发挥了重要的调控作用。miRNA可以通过沉默或诱导靶基因表达参与颗粒细胞功能、卵母细胞成熟和卵泡发育的调控；lncRNA作为miRNA的分子海绵，通过竞争性结合miRNA间接调控基因表达，影响卵泡内的生殖细胞发育和卵巢功能。作者综述了miRNA和lncRNA在反刍动物卵泡发育中的分子功能和作用机制，并对miRNA、lncRNA和基因三者之间的竞争性内源RNA(competing endogenous RNA,ceRNA)互作网络进行归纳，为挖掘母畜繁殖力性状关键基因和分子育种工作提供可靠的基因资源和理论参考。

关键词: miRNA; lncRNA; ceRNA互作机制; 反刍动物; 卵泡发育

Abstract: Follicular development is an important factor in determining ovulation rate and lambing number，it directly affects the reproductive function and fecundity of maternal animals.With the development of omics technology in recent years,microRNA (miRNA) and long non-coding RNA (lncRNA) have played an important regulatory role in the dynamic development of follicle in ruminants.miRNA can participate in the regulation of granulosa cell function,oocyte maturation and follicular development by silencing or inducing the expression of target genes.lncRNA acts as a molecular sponge for miRNA and indirectly regulates gene expression by competitive binding to miRNA,affecting germ cell development and ovarian function within the follicle.The authors review the molecular function and mechanism of miRNA and lncRNA in follicle development of ruminants,and summarize the competitive endogenous RNA (ceRNA) interaction networks among miRNA,lncRNA and gene,in order to provide a reliable genetic resources and theoretical reference for excavating key genes for reproductive traits of maternal animals and carrying out molecular breeding work.

Key words: miRNA; lncRNA; ceRNA interaction mechanism; ruminants; follicular development

中图分类号:

S814

王泳, 马驰, 王超, 赵启南, 孙智鹏, 田丰, 王利, 金海, 李长青. miRNA和lncRNA调控反刍动物卵泡发育的分子机制研究进展[J]. 中国畜牧兽医, 2025, 52(2): 771-780.

WANG Yong, MA Chi, WANG Chao, ZHAO Qinan, SUN Zhipeng, TIAN Feng, WANG Li, JIN Hai, LI Changqing. Research Progress on Molecular Mechanism of miRNA and lncRNA Regulating Follicular Development in Ruminants[J]. China Animal Husbandry and Veterinary Medicine, 2025, 52(2): 771-780.

参考文献

[1] SLACK F J,CHINNAIYANX A M.The role of non-coding RNAs in oncology[J]. Cell,2019,179(5):1033-1055.
[2] GLADYS J.Genomic structural variation and schizophrenia[J].Current Psychiatry Reports,2008,10(2):171-177.
[3] ZHUO Z,WANG C,YU H.Plasma microRNAs can be a potential diagnostic biomarker for endometriosis[J].Ginekologia Polska,2022,93(6):450-459.
[4] WEI Q,LI J,HE H,et al.miR-23b-3p inhibits chicken granulosa cell proliferation and steroid hormone synthesis via targeting GDF9[J].Theriogenology,2022,177:84-93.
[5] GAO L,ZHANG L,ZHANG Y,et al.miR-10a-5p inhibits steroid hormone synthesis in porcine granulosa cells by targeting CREB1 and inhibiting cholesterol metabolism[J].Theriogenology,2023,212:19-29.
[6] YU C,LIN Z,SONG X,et al.Whole transcriptome analysis reveals the key genes and noncoding RNAs related to follicular atresia in broilers[J].Animal Biotechnology,2023,34(7):3144-3153.
[7] LEE R C,FEINBAUM R L,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.
[8] LAGOS Q M,RAUHUT R,LENDECKEL W,et al.Identification of novel genes coding for small expressed RNAs[J].Science,2001,294(5543):853-858.
[9] LAU N C,LIM L P,WEINSTEIN E G,et al.An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans[J].Science,2001,294(5543):858-862.
[10] LEE R C,AMBROS V.An extensive class of small RNAs in Caenorhabditis elegans[J].Science,2001,294(5543):862-864.
[11] YEUNG M L,BENNASER Y,WATASHI K,et al.Pyrosequencing of small non-coding RNAs in HIV-1 infected cells:Evidence for the processing of a viral-cellular double-stranded RNA hybrid[J].Nucleic Acids Research,2009,37(19):6575-6586.
[12] BOHNSACK M T,CZAPLINSKI K,GORLICH D.Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs[J].RNA,2004,10(2):185-191.
[13] GREGORY R I,CHENDRIMADA T P,COOCH N,et al.Human RISC couples microRNA biogenesis and posttranscriptional gene silencing[J].Cell,2005,123(4):631-640.
[14] LIN S,GREGORY R I.microRNA biogenesis pathways in cancer[J].NatureReviews Cancer,2015,15(6):321-333.
[15] XU G,MENG Y,WANG L,et al.miRNA-214-5p inhibits prostate cancer cell proliferation by targeting SOX4[J].World Journal of Surgical Oncology,2021,19(1):338.
[16] LIU J,LIANG Y,QIAO L,et al.miR-128-1-5p regulates differentiation of ovine stromal vascular fraction by targeting the KLF115'-UTR[J].Domestic Animal Endocrinology,2022,80:106711.
[17] VASCHETTO L M.miRNA activation is an endogenous gene expression pathway[J].RNA Biology,2018,15(6):826-828.
[18] LI L C,OKINO S T,ZHAO H,et al.Small dsRNAs induce transcriptional activation in human cells[J].Proceedings of the National Academy of Sciences of the United States of America,2006,103(46):17337-17342.
[19] HUANG V,PLACE R F,PORTNOY V,et al.Upregulation of Cyclin B1 by miRNA and its implications in cancer[J].Nucleic Acids Research,2012,40(4):1695-1707.
[20] CHALUVALLY R P,JEONG K J,PRADEEP S,et al.Direct upregulation of STAT3 by microRNA-551b-3p deregulates growth and metastasis of ovarian cancer[J].Cell Reports,2016,15(7):1493-1504.
[21] PEPLING M E,SPRADLING A C.Mouse ovarian germ cell cysts undergo programmed breakdown to form primordial follicles[J].Developmental Biology,2001,234(2):339-351.
[22] MENKE D B,KOUBOVA J,PAGE D C.Sexual differentiation of germ cells in XX mouse gonads occurs in an anterior-to-posterior wave[J].Developmental Biology,2003,262(2):303-312.
[23] EPPIG J J.Oocyte control of ovarian follicular development and function in mammals[J].Reproduction,2001,122(6):829-838.
[24] EDSON M A,NAGARAJA A K,MATZUK M M.The mammalian ovary from genesis to revelation[J].Endocrine Reviews,2009,30(6):624-712.
[25] DIAZ F J,WIGGLESWORTH K,EPPIG J J.Oocytes are required for the preantral granulosa cell to cumulus cell transition in mice[J].Developmental Biology,2007,305(1):300-311.
[26] MCBTIDE D,CARR W,SONTAKKE S D,et al.Identification of miRNAs associated with the follicular luteal transition in the ruminant ovary[J].Reproduction,2012,144(2):221.
[27] LING Y H,REN C H,GUO X F,et al.Identification and characterization of microRNAs in the ovaries of multiple and uniparous goats (Capra hircus) during follicular phase[J].BMC Genomics,2014,15(1):339.
[28] YUAN H,LU J,XIAO S Y,et al.miRNA expression analysis of the sheep follicle during the prerecruitment,dominant,and mature stages of development under FSH stimulation[J].Theriogenology,2022,181:161-169.
[29] SONTAKKE S D,MOHAMMED B T,MCNEILLY A S,et al.Characterization of microRNAs differentially expressed during bovine follicle development[J].Reproduction,2014,148(3):271-283.
[30] SALILEW-WONDIM D,AHMAD I,GEBREMEDHN S,et al.The expression pattern of microRNAs in granulosa cells of subordinate and dominant follicles during the early luteal phase of the bovine estrous cycle[J].PLoS One,2014,9(9):e106795.
[31] TESFAYE D,WORKU D,RINGS F,et al.Identification and expression profiling of microRNAs during bovine oocyte maturation using heterologous approach[J].Molecular Reproduction and Development,2009,76(7):665-677.
[32] ABD EL NABY W S,HAGOS T H,HOSSAIN M M,et al.Expression analysis of regulatory microRNAs in bovine cumulus oocyte complex and preimplantation embryos[J].Zygote,2013,21(1):31-51.
[33] GUO Y,TONG X,TANG P,et al.Nourishing kidney promoting ovulation decoction (NKPOD) attenuates polycystic ovary syndrome by downregulating miRNA-224[J].Evidence-Based Complementary and Alternative Medicine,2023,2023:9402155.
[34] ZHANG T,HUO S,WEI S,et al.miR-21,miR-125b,and let-7b contribute to the involution of atretic follicles and corpus lutea in Tibetan sheep ovaries[J].Animal Science Journal,2022,93(1):e13756.
[35] GUI H,LI F,CHEN C,et al.miR-27a-3p targets NR5A2 to regulate CYP19A1 expression and 17-β estradiol synthesis in ovine granulosa cells[J].Animal Reproduction Science,2023,248:107160.
[36] FENG G,LIU J,LU Z,et al.miR-450-5p and miR-202-5p synergistically regulate follicle development in Black goat[J].International Journal of Molecular Sciences,2022,24(1):401.
[37] ZHOU R Y,MIAO Y P,LI Y M,et al.microRNA-150 promote apoptosis of ovine ovarian granulosa cells by targeting STAR gene[J].Theriogenology,2019,127:66-71.
[38] GUO L,XU H,LI Y,et al.Kisspeptin-10 promotes progesterone synthesis in bovine ovarian granulosa cells via downregulation of microRNA-1246[J].Genes,2022,13(2):298.
[39] ZHANG Z,CHEN C Z,XU M Q,et al.miR-31 and miR-143 affect steroid hormone synthesis and inhibit cell apoptosis in bovine granulosa cells through FSHR[J].Theriogenology,2019,123:45-53.
[40] WANG L,HAND J M,FU L,et al.DNA methylation and miRNA-1296 act in concert to mediate spatiotemporal expression of KPNA7 during bovine oocyte and early embryonic development[J].BMC Developmental Biology,2019,19(1):23.
[41] DERRIEN T,JOHNSON R,BUSSOTTI G,et al.The GENCODE v7 catalog of human long noncoding RNAs:Analysis of their gene structure,evolution,and expression[J].Genome Research,2012,22(9):1775-1789.
[42] CABILI M N,DUNAGIN M C,MCCLANAHAN P D,et al.Localization and abundance analysis of human lncRNAs at single-cell and single-molecule resolution[J].Genome Biology,2015,16(1):20.
[43] CABILI M N,TRAPNELL C,GOFF L,et al.Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses[J].Genes & Development,2011,25(18):1915-1927.
[44] LIU S J,HORLBECK M A,CHO S W,et al.CRISPRi-based genome-scale identification of functional long noncoding RNA loci in human cells[J].Science,2017,355(6320):eaah7111.
[45] BRIDGES M C,DAULAGALA A C,KOURTIDIS A.Lnccation:lncRNA localization and function[J].Journal of Cell Biology,2021,220(2):e202009045.
[46] MIAO H,WANG L,ZHAN H,et al.A long noncoding RNA distributed in both nucleus and cytoplasm operates in the PYCARD-regulated apoptosis by coordinating the epigenetic and translational regulation[J].PLoS Genetics,2019,15(5):e1008144.
[47] SALMENA L,POLLISENO L,TAY Y,et al.A ceRNA hypothesis:The rosetta stone of a hidden RNA language?[J].Cell,2011,146(3):353-358.
[48] LUO H,XU C,LE W,et al.lncRNA CASC11 promotes cancer cell proliferation in bladder cancer through miRNA-150[J].Journal of Cellular Biochemistry,2019,120(8):13487-13493.
[49] BAO D,YUAN R X,ZHANG Y.Effects of lncRNA MEG3 on proliferation and apoptosis of gallbladder cancer cells through regulating NF-κB signaling pathway[J].European Review for Medical & Pharmacological Sciences,2020,24(12):6632-6638.
[50] TU J,CHEN Y,LI Z,et al.Long non-coding RNAs in ovarian granulosa cells[J].Journal of Ovarian Research,2020,13(1):63.
[51] CHEN J,WANG Y,WANG C,et al.lncRNA functions as a new emerging epigenetic factor in determining the fate of stem cells[J].Frontiers in Genetics,2020,11:277.
[52] LIAO J,CHEN B,ZHU Z,et al.Long noncoding RNA (lncRNA) H19:An essential developmental regulator with expanding roles in cancer,stem cell differentiation,and metabolic diseases[J].Genes & Diseases,2023,10(4):1351-1366.
[53] CARNINCI P,HAYASHIZAKI Y.Noncoding RNA transcription beyond annotated genes[J].Current Opinion in Genetics & Development,2007,17(2):139-144.
[54] EWAN B,JOHN A S,ANINDYA D,et al.Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project[J].Nature,2007,447(7146):799-816.
[55] KAPRANOV P,CHENG J,DIKE S,et al.RNA maps reveal new RNA classes and a possible function for pervasive transcription[J].Science,2007,316(5830):1484-1488.
[56] HERMAN A B,TSITSIPATIS D,GOROSPE M.Integrated lncRNA function upon genomic and epigenomic regulation[J].Molecular Cell,2022,82(12):2252-2266.
[57] SUN M,KRAUS W L.From discovery to function:The expanding roles of long noncoding RNAs in physiology and disease[J].Endocrine Reviews,2015,36(1):25-64.
[58] ZHANG L,ZOU J,WANG Z,et al.A subpathway and target gene cluster-based approach uncovers lncRNAs associated with human primordial follicle activation[J].International Journal of Molecular Sciences,2023,24(13):10525.
[59] LI J,CAO Y,XU X,et al.Increased new lncRNA-mRNA gene pair levels in human cumulus cells correlate with oocyte maturation and embryo development[J].Reproductive Sciences,2015,22(8):1008-1014.
[60] ELMONIER A A,EL-BOGHDADY N A,FAHIM S A,et al.lncRNA NEAT1 and MALAT1 are involved in polycystic ovary syndrome pathogenesis by functioning as competing endogenous RNAs to control the expression of PCOS-related target genes[J].Non-coding RNA Research,2023,8(2):263-271.
[61] SUN D,WANG Y,SUN N,et al.lncRNA DANCR counteracts premature ovarian insufficiency by regulating the senescence process of granulosa cells through stabilizing the interaction between p53 and hNRNPC[J].Journal of Ovarian Research,2023,16(1):41.
[62] MIAO X,LUO Q,ZHAO H,et al.Co-expression analysis and identification of fecundity-related long non-coding RNAs in sheep ovaries[J].Scientific Reports,2016,6(1):39398.
[63] LIU A,LIU M,LI Y,et al.Differential expression and prediction of function of lncRNAs in the ovaries of low and high fecundity Hanper sheep[J].Reproduction in Domestic Animals,2021,56(4):604-620.
[64] YAO X L,YANG F,EL-SAMAHY M A,et al.Identification and characterization of unique and common lncRNAs and mRNAs in the pituitary,ovary,and uterus of Hu sheep with different prolificacy[J].Genomics,2022,114(6):110511.
[65] LI M H,NIU M H,FENG Y Q,et al.Establishment of lncRNA-mRNA network in bovine oocyte between germinal vesicle and metaphase Ⅱ stage[J].Gene,2021,791:145716.
[66] CAI M D,XU Z Q,LIU Y H,et al.lncRNA-mediated effects of vitrification temperatures and cryoprotectant concentrations on bovine oocyte development following vitrification at the GV stage[J].Theriogenology,2022,186:135-145.
[67] CLAIRE L S,TAMARA S,CHRIS P P.Complexities of post-transcriptional regulation and the modeling of ceRNA crosstalk[J].Critical Reviews in Biochemistry & Molecular Biology,2018,53(3):231-245.
[68] CHEN H,CHENG S,XIONG W,et al.The lncRNA-miRNA-mRNA ceRNA network in mural granulosa cells of patients with polycystic ovary syndrome:an analysis of gene expression omnibus data[J].Annals of Translational Medicine,2021,9(14):1156.
[69] SU L,ZHANG Y,WANG Y,et al.Identification of a lncRNA/circRNA-miRNA-mRNA ceRNA network in Alzheimer’s disease[J].Journal of Integrative Neuroscience,2023,22(6):136.
[70] SADEHGI M,BAHRAMI A,HASANKHANI A,et al.lncRNA-miRNA-mRNA ceRNA network involved in sheep prolificacy:An integrated approach[J].Genes,2022,13(8):1295.
[71] SÁNCHEZ F,SMITZ J.Molecular control of oogenesis[J].Biochimica et Biophysica Acta,2012,1822(12):1896-1912.
[72] LIU J B,ZHANG J B,YAN X M,et al.DNA double-strand break-related competitive endogenous RNA network of noncoding RNA in bovine cumulus cells[J].Genes,2023,14(2):290.
[73] ZHAO L,PAN Y,WANG M,et al.Integrated analysis of the expression profiles of the lncRNA-miRNA-mRNA ceRNA network in granulosa and cumulus cells from yak ovaries[J].BMC Genomics,2022,23(1):633.
[74] WANG L,CHO K B,LI Y,et al.Long noncoding RNA (lncRNA)-mediated competing endogenous RNA networks provide novel potential biomarkers and therapeutic targets for colorectal cancer[J].International Journal of Molecular Sciences,2019,20(22):5758.
[75] KERWIN J,KHAN I.Replication study:A coding-independent function of gene and pseudogene mRNAs regulates tumour biology[J].eLife,2020,9:e51019.
[76] YAO X,GAO X X,BAO Y,et al.lncRNA FDNCR promotes apoptosis of granulosa cells by targeting the miR-543-3p/DCN/TGF-β signaling pathway in Hu sheep[J].Molecular Therapy-Nucleic Acids,2021,24:223-240.
[77] YAO X,EL-SAMAHY M A F,LI X,et al.lncRNA-412.25 activates the LIF/STAT3 signaling pathway in ovarian granulosa cells of Hu sheep by sponging miR-346[J].FASEB Journal,2022,36(9):e22467.
[78] WANG Y,GUO Y,DUAN C,et al.lncGSAR controls ovarian granulosa cell steroidogenesis via sponging miR-125b to activate SCAP/SREBP pathway[J].International Journal of Molecular Sciences,2022,23(20):12132.
[79] YAO Y,WANG Y,WANG F,et al.BMP15 modulates the H19/miR-26b/SMAD1 axis influences yak granulosa cell proliferation,autophagy,and apoptosis[J].Reproductive Sciences,2023,30(4):1266-1280.
[80] HAN X,PAN Y,FAN J,et al.lncRNA MEG3 regulates ASK1/JNK axis-mediated apoptosis and autophagy via sponging miR-23a in granulosa cells of yak tertiary follicles[J].Cellular Signalling,2023,107:110680.
[81] YANG Z W,PAN J X,ZHOU C L,et al.lncRNA SNHG5 adversely governs follicular growth in PCOS via miR-92a-3p/CDKN1C axis[J].iScience,2023,27(2):108522.
[82] XU X M,YIN C,DONG B,et al.lncRNA XIST protects against polycystic ovary syndrome via the regulation of miR-212-3p/RASA1 axis[J].Biochemical Genetics,2024.Doi:10.1007/s10528-024-10777-7.Online ahead of print.
[83] SHEN C M H,CHEN T,HE G T,et al.lncRNA LOC102163816 promotes proliferation of porcine follicular granulosa cells via miR-455-3p/PTK2B/PI3K/Akt pathway[J].Endocrinology,2024,165(3):bqae007.