LncRNAs与miRNAs在非梗阻性无精症中的研究进展
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摘要
非梗阻性无精症(non-obstructive azoospermia,NOA)约占男性不育的10%～15%。然而,非染色体性NOA病因复杂,发病机制尚不清楚。精子生成过程受到转录因子、基因或信号通路的调控。其中长链非编码RNAs(lncRNAs)为长度大于200个核苷酸的调控性非编码RNA,通过转录、转录后修饰和表观遗传水平等多种机制调节基本的生化和细胞过程。微小RNAs(miRNAs)通过碱基互补配对的形式与mRNA结合,促使mRNA降解或阻碍其翻译,进而抑制目的蛋白的表达,在多种生物过程中发挥作用,包括发育、分化、细胞增殖和细胞凋亡。LncRNAs与miRNAs的异常表达可导致精子正常发育过程的紊乱。深入研究NOA相关的lncRNAs与miRNAs及其作用机制,有助于探讨NOA的病因和发病机制。
Non-obstructive azoospermia(NOA) accounts for about 10% to 15% of male infertility.However, the etiology of non-chromosomal NOA is complex and the pathogenesis is still unclear. Spermatogenesis is regulated by transcription factors, genes or signaling pathways. Long non-coding RNAs(lncRNAs) are a kind of regulatory non-coding RNAs with a length of more than 200 nucleotides, which participate in basic biochemical and cellular processes through various mechanisms such as transcription, post-transcriptional and epigenetic modification. MicroRNAs(miRNAs) bind to mRNA through base-pairing, in which miRNAs promote mRNA degradation or block mRNA translation, and inhibite the expression of the target protein. MiRNAs play multiple roles in biological processes including development, differentiation, cell proliferation and apoptosis. The abnormal expressions of lncRNAs and miRNAs can lead to the disorder of spermatogenesis. Therefore, the study on lncRNAs and miRNAs in NOA is helpful for us to analyse the etiology and pathogenesis of NOA.
Non-obstructive azoospermia(NOA) accounts for about 10% to 15% of male infertility.However, the etiology of non-chromosomal NOA is complex and the pathogenesis is still unclear. Spermatogenesis is regulated by transcription factors, genes or signaling pathways. Long non-coding RNAs(lncRNAs) are a kind of regulatory non-coding RNAs with a length of more than 200 nucleotides, which participate in basic biochemical and cellular processes through various mechanisms such as transcription, post-transcriptional and epigenetic modification. MicroRNAs(miRNAs) bind to mRNA through base-pairing, in which miRNAs promote mRNA degradation or block mRNA translation, and inhibite the expression of the target protein. MiRNAs play multiple roles in biological processes including development, differentiation, cell proliferation and apoptosis. The abnormal expressions of lncRNAs and miRNAs can lead to the disorder of spermatogenesis. Therefore, the study on lncRNAs and miRNAs in NOA is helpful for us to analyse the etiology and pathogenesis of NOA.
引文
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[2]杜琛,徐琰琪,陈秀娟.非编码RNA在生殖调节中的研究进展[J].国际生殖健康/计划生育杂志,2016,35(4):344-347.
[3]Wu Z,Liu X,Liu L,et al.Regulation of lncRNA expression[J].Cell Mol Biol Lett 2014,19(4):561-575.
[4]Wang KC,Chang HY.Molecular Mechanisms of Long Noncoding RNAs[J].Molecular Cell,2011,43(6):904-914.
[5]Cabili MN,Trapnell C,Goff L,et al.Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses[J].Genes Dev,2011,25(18):1915-1927.
[6]Noh JH,Kim KM,McClusky WG,et al.Cytoplasmic functions of long noncoding RNAs[J].Wiley Interdiscip Rev RNA,2018,9(3):e1471.
[7]LüM,Tian H,Cao YX,et al.Downregulation of miR-320a/383-sponge-like long non-coding RNA NLC1-C(narcolepsy candidate-region 1 genes)is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation[J].Cell Death Dis,2015,6:e1960.
[8]Li L,Wang M,Wu X,et al.A long non-coding RNA interacts with Gfra1 and maintains survival of mouse spermatogonial stem cell[J].Cell Death Dis,2016,7:e2140.
[9]Hu K,Zhang J,Liang M.LncRNA AK015322 promotes proliferation of spermatogonial stem cell C18-4 by acting as a decoy for microRNA-19b-3p[J].In Vitro Cell Dev Biol Anim,2017,53(3):277-284.
[10]Zhou W,Shao H,Zhang D,et al.PTEN signaling is required for the maintenance of spermatogonial stem cells in mouse,by regulating the expressions of PLZF and UTF1[J].Cell Biosci,2015,5:42.
[11]Hu K,Li L,Liao Y,et al.LncRNA Gm2044 highly expresses in spermatocyte and inhibits Utf1 translation by interacting with Utf1m RNA[J].Genes Genomics,2018,40(7):781-787.
[12]Yoneda R,Satoh Y,Yoshida I,et al.A genomic region transcribed into a long noncoding RNA interacts with the Prss42/Tessp-2promoter in spermatocytes during mouse spermatogenesis,and its flanking sequences can function as enhancers[J].Mol Reprod Dev,2016,83(6):541-557.
[13]Zhao J,Li H,Deng H,et al.LncRNA gadd7,increased in varicocele patients,suppresses cell proliferation and promotes cell apoptosis[J].Oncotarget,2017,9(4):5105-5110.
[14]Jiménez-Badillo SE,Oviedo N,Hernández-Guzmán C,et al.Catsper1 promoter is bidirectional and regulates the expression of a novel lncRNA[J].Sci Rep,2017,7(1):13351.
[15]Thomas M,Lieberman J,Lal A.Desperately seeking microRNAtargets[J].Nat Struct Mol Biol,2010,17(10):1169-1174.
[16]Romero Y,Meikar O,Papaioannou MD,et al.Dicer1 depletion in male germ cells leads to infertility due to cumulative meiotic and spermiogenic defects[J].PLoS One,2011 6(10):e25241.
[17]符梅,徐克惠,叶俊杰,等.miRNA成熟关键基因DROSHA和DICER的多态性与无精症的相关性[J].中华医学遗传学杂志,2016,33(3):365-368.
[18]Yadav RP,Kotaja N.Small RNAs in spermatogenesis[J].Mol Cell Endocrinol,2014,382(1):498-508.
[19]Yao CC,Yuan QQ,Niu MH,et al.Distinct Expression Profiles and Novel Targets of MicroRNAs in Human Spermatogonia,Pachytene Spermatocytes,and Round Spermatids between OA Patients and NOA Patients[J].Mol Ther Nucleic Acids,2017,9(15):182-194.
[20]Lian J,Zhang X,Tian H,et al.Altered microRNA expression in patients with non-obstructive azoospermia[J].Reprod Biol Endocrinol,2009,7:13.
[21]Marcon E,Babak T,Chua G,et al.miRNA and piRNA localization in the male mammalian meiotic nucleus[J].Chromosome Res,2008,16(2):243-260.
[22]Song WY,Meng H,Wang XG,et al.Reduced microRNA-188-3p expression contributes to apoptosis of spermatogenic cells in patients with azoospermia[J].Cell Prolif,2017,50(1):e12297.
[23]Xu M,Hecht NB.Polypyrimidine tract‐binding protein 2 binds to selective,intronic messenger RNA and microRNA targets in the mouse testis[J].Biol Reprod,2011,84:435-439.
[24]Fang N,Cao C,Wen Y,et al.MicroRNA profile comparison of testicular tissues derived from successful and unsuccessful microdissection testicular sperm extraction retrieval in nonobstructive azoospermia patients[J].Reprod Fertil Dev,2018,[Epub ahead of print].
[25]Wu J,Bao J,Kim M,et al.Two miRNA clusters,miR-34b/c and miR-449,are essential for normal brain development,motile ciliogenesis,and spermatogenesis[J].Proc Natl Acad Sci U S A,2014,111(28):E2851-E2857.
[26]Salmena L,Poliseno L,Tay Y,et al.A ceRNA hypothesis:the Rosetta Stone of a hidden RNA language?[J].Cell,2011,146(3):353-358.
[27]Wang F,Yang H,Deng Z,et al.HOX Antisense lincRNA HOXA-AS2 Promotes Tumorigenesis of Hepatocellular Carcinoma[J].Cell Physiol Biochem,2016,40(1/2):287-296.
[28]Vennin C,Spruyt N,Dahmani F,et al.H19 non coding RNA-derived miR-675 enhances tumorigenesis and metastasis of breast cancer cells by downregulating c-Cbl and Cbl-b[J].Oncotarget,2015,6(30):29209-29223.
[29]Cai X,Cullen BR.The imprinted H19 noncoding RNA is a primary microRNA precursor[J].RNA,2007,13(3):313-316.
[30]Ballantyne MD,McDonald RA,Baker AH.lncRNA/MicroRNAinteractions in the vasculature[J].Clin Pharmacol Ther,2016,99(5):494-501.
[31]Gernapudi R,Wolfson B,Zhang Y,et al.MicroRNA 140 Promotes Expression of Long Noncoding RNA NEAT1 in Adipogenesis[J].Mol Cell Biol,2015,36(1):30-38.