Lin28对哺乳动物生殖调控的研究进展
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摘要
Lin28a和Lin28b是RNA结合蛋白,通过结合let-7 microRNA前体调控let-7的成熟过程,或直接与mRNA结合调控其翻译和稳定性,参与细胞多潜能性、肿瘤发生、葡萄糖代谢等多个生理过程。最近一些研究发现二者可能参与人和动物的生殖活动,但功能还不清晰。本文对Lin28a和Lin28b基因在哺乳动物初情期启动、原始生殖细胞(primordial germ cells, PGCs)形成和配子发生中的作用相关研究进行了综述,以期为深入探索二者在动物生殖中的功能研究提供参考。
Lin28a and Lin28 b, as RNA-binding proteins, bind to the terminal loop of pri-and pre-let-7miRNA and repress their processing; also bind to target mRNA to modulate their translation, and mediate several physiological processes, such as cell pluripotency maintenance, tumorigenesis and glucose metabolism. Some new researches discovered that Lin28 a and Lin28 b may participate in human and animal reproduction, and the action mechanisms remain ill defined. The present paper reviews the research progress on the role of Lin28 a and Lin28 b genes in onset of mammalian puberty, primordial germ cell(PGCs)formation and gametogenesis, and provide some reference for further studies on their roles in animal reproduction.
Lin28a and Lin28 b, as RNA-binding proteins, bind to the terminal loop of pri-and pre-let-7miRNA and repress their processing; also bind to target mRNA to modulate their translation, and mediate several physiological processes, such as cell pluripotency maintenance, tumorigenesis and glucose metabolism. Some new researches discovered that Lin28 a and Lin28 b may participate in human and animal reproduction, and the action mechanisms remain ill defined. The present paper reviews the research progress on the role of Lin28 a and Lin28 b genes in onset of mammalian puberty, primordial germ cell(PGCs)formation and gametogenesis, and provide some reference for further studies on their roles in animal reproduction.
引文
Aeckerle N,Eildermann K,rummer C D,et al.2012.The pluripotency factor LIN28 in monkey and human testes:Amarker for spermatogonial stem cells?[J].Molecular Human Reproduction,18(10):477-488.
Ambros V A.1989.A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C.elegans[J].Cell,57(1):49-57.
Assou S,Cerecedo D,Tondeur S,et al.2009.A gene expression signature shared by human mature oocytes and embryonic stem cells[J].BMC Genomics,10(1):10.
Cao D,Allan R W,Cheng L,et al.2011.RNA-binding protein LIN28 is a marker for testicular germ cell tumors[J].Human Pathology,42(5):710-718.
Chatterji P,Rustgi A K.2018.RNA binding proteins in intestinal epithelial biology and colorectal cancer[J].Trends in Molecular Medicine,24(5):490-506.
Childs A J,Kinnell H L,He J,et al.2012.LIN28 is selectively expressed by primordial and pre-meiotic germ cells in the human fetal ovary[J].Stem Cells and Development,21(13):2343-2349.
Corre C,Shinoda G,Zhu H,et al.2016.Sex-specific regulation of weight and puberty by the Lin28/let-7 axis[J].Journal of Endocrinology,228(3):179-191.
El-Khairi R,Parnaik R,Duncan A J,et al.2012.Analysis of LIN28A in early human ovary development and as a candidate gene for primary ovarian insufficiency[J].Molecular and Cellular Endocrinology,351(2):264-268.
Elks C E,Perry J R,Sulem P,et al.2010.Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies[J].Nature Genetics,42(12):1077-1087.
Faas L,Warrander F C,Maguire R,et al.2013.Lin28 proteins are required for germ layer specification in Xenopus[J].Development,140(5):976-986.
Farzaneh M,Attari F,Khoshnam S E.2017.Concise review:LIN28/let-7 signaling,a critical double-negative feedback loop during pluripotency,reprogramming,and tumorigenicity[J].Cell Reprogram,19(5):289-293.
Gaytan F,Sangiao-Alvarellos S,Manfredi-Lozano M,et al.2013.Distinct expression patterns predict differential roles of the miRNA-binding proteins,Lin28 and Lin28b,in the mouse testis:Studies during postnatal development and in a model of hypogonadotropic hypogonadism[J].Endocrinology,154(3):1321-1336.
Gillis A J,Stoop H,Biermann K,et al.2011.Expression and interdependencies of pluripotency factors LIN28,OCT3/4,NANOG and SOX2 in human testicular germ cells and tumours of the testis[J].International Journal of Andrology,34(4 pt 2):e160-e174.
Grieco A,Rzeczkowska P,Alm C,et al.2013.Investigation of peripubertal expression of Lin28a and Lin28b in C57BL/6 female mice[J].Molecular and Cellular Endocrinology,365(2):241-248.
Guo Y,Chen Y,Ito H,et al.2006.Identification and characterization of lin-28 homolog B(LIN28B)in human hepatocellular carcinoma[J].Gene,384(24):51-61.
Hanna J,Saha K,Pando B,et al.2009.Direct cell reprogramming is a stochastic process amenable to acceleration[J].Nature,462(7273):595-601.
He C,Kraft P,Chen C,et al.2009.Genome-wide association studies identify loci associated with age at menarche and age at natural menopause[J].Nature Genetics,41(6):724-728.
Hu Z,Chen R,Cai C.2016.Association of genetic polymorphisms around the LIN28B gene and idiopathic central precocious puberty risks among Chinese girls[J].Pediatric Research,80(4):521-525.
Lee W Y,Park H J,Lee R,et al.2017.Analysis of putative biomarkers of undifferentiated spermatogonia in dog testis[J].Animal Reproduction Science,185:174-180.
Lettre G,Jackson A U,Gieger C,et al.2008.Identification of ten loci associated with height highlights new biological pathways in human growth[J].Nature Genetics,40(5):584-591.
M?kel?J A,Toppari J,Riveromüller A,et al.2014.Reconstruction of mouse testicular cellular microenvironments in long-term seminiferous tubule culture[J].PLoS One,9(3):e90088.
Martins S,Bohndorf M,Schr?ter F,et al.2017.Lymphob last-derived integration-free ISRM-CON9 iPS cell line from a 75 year old female[J].Stem Cell Research,26:76-79.
Matzuk M M.2009.LIN28 lets BLIMP1 take the right course[J].Developmental Cell,17(2):160-161.
Moss E G,Lee R C,Ambros V.1997.The cold shock domain protein LIN28 controls developmental timing in C.elegans and is regulated by the lin-4 RNA[J].Cell,88(5):637-646.
Moss E G,Tang L.2003.Conservation of the heterochronic regulator Lin-28,its developmental expression and microRNA complementary sites[J].Developmental Biology,258(2):432-442.
Murray M J,Saini H K,Siegler C A,et al.2013.LIN28 Expression in malignant germ cell tumors downregulates let-7 and increases oncogene levels[J].Cancer Research,73(15):4872-4884.
Ong K K,Elks C E,Li S,et al.2009.Genetic variation in LIN28B is associated with the timing of puberty[J].Nature Genetics,41(6):729-733.
Ouchi Y,Yamamoto J,Iwamoto T.2014.The heterochronic genes lin-28a and lin-28b play an essential and evolutionarily conserved role in early zebrafish development[J].PLoS One,9(2):e88086.
Park G T,Seo Y M,Lee S Y,et al.2012.Lin28 regulates the expression of neuropeptide Y receptors and oocyte-specific homeobox genes in mouse embryonic stem cells[J].Clinical and Experimental Reproductive Medicine,39(2):87-93.
Perry J R B,Stolk L,Franceschini N,et al.2009.Meta-analysis of genome-wide association data identifies two loci influencing age at menarche[J].Nature Genetics,41(6):648-650.
Sangiao-Alvarellos S,Manfredi-Lozano M,Ruiz-Pino F,et al.2013.Changes in hypothalamic expression of the Lin28/let-7 system and related microRNAs during postnatal maturation and after experimental manipulations of puberty[J].Endocrinology,154(2):942-955.
Sangiao-Alvarellos S,Manfredi-Lozano M,Ruiz-Pino F,et al.2015.Testicular expression of the Lin28/let-7 system:Hormonal regulation and changes during postnatal maturation and after manipulations of puberty[J].Scientific Reports,5:15683.
Shinoda G,Shyh-Chang N,de Soysa T,et al.2013.Fetal deficiency of lin28 programs life-long aberrations in growth and glucose metabolism[J].Stem Cells,31(8):1563-1573.
Silveira-neto A P,Leal L F,Emerman A B,et al.2012.Absence of functional LIN28B futations in a large cohort of patients with idiopathic central precocious puberty[J].Hormone Research in Paediatrics,78(3):144-150.
Srivastava V K,Hiney J K,Stevener K,et al.2015.Differential effects of alcohol on excitatory and inhibitory puberty-related peptides in the basal hypothalamus of the female rat[J].Alcoholism:Clinical and Experimental Research,39(12):2386-2393.
Stratoulias V,Heino T I,Michon F.2014.Lin-28 regulates oogenesis and muscle formation in Drosophila melanogaster[J].PLOS One,9(6):e101141.
Sulem P,Gudbjartsson D F,Rafnar T,et al.2009.Genomewide association study identifies sequence variants on6q21 associated with age at menarche[J].Nature Genetics,41(6):734-738.
Thornton J E,Gregory R I.2012.How does Lin28 let-7 control development and disease?[J]Trends in Cell Biology,22(9):474-482.
Tommiska J,S?rensen K,Aksglaede L,et al.2011.LIN28B,LIN28A,KISS1,and KISS1R in idiopathic central precocious puberty[J].BMC Research Notes,4(1):363-363.
Urbach A,Yermalovich A,Zhang J,et al.2014.Lin28 sustains early renal progenitors and induces Wilms tumor[J].Genes&Development,28(9):971-982.
Virant-Klun I,Skutella T,Stimpfel M,et al.2011.Ovarian surface epithelium in patients with severe ovarian infertility:A potential source of cells expressing markers of pluripotent/multipotent stem cells[J].Journal of Biomedicine and Biotechnology,2011:381928.
Viswanathan S R,Powers J T,Einhorn W,et al.2009.Lin28promotes transformation and is associated with advanced human malignancies[J].Nature Genetics,41(7):843-848.
Voutsadakis I A.2018.The pluripotency network in colorectal cancer pathogenesis and prognosis:An update[J].Biomarkers in Medicine,12(6):653-665.
Widén E,Ripatti S,Cousminer D L,et al.2010.Distinct variants at LIN28B influence growth in height from birth to adulthood[J].The American Journal of Human Genetics,86(5):773-782.
West J A,Viswanathan S R,Yabuuchi A,et al.2009.A role for Lin28 in primordial germ-cell development and germ-cell malignancy[J].Nature,460(7257):909-914.
Werler S,Demond H,Damm O S,et al.2014.Germ cell loss is associated with fading Lin28a expression in a mouse model for Klinefelter's syndrome[J].Reproduction,147(3):253-264
Yang D H,Moss E G.2003.Temporally regulated expression of Lin-28 in diverse tissues of the developing mouse[J].Gene Expression Pattern,3(6):719-726.
Yang M,Yang S L,Herrlinger S,et al.2015.Lin28 promotes the proliferative capacity of neural progenitor cells in brain development[J].Development,142(9):1616-1627.
Yu J,Vodyanik M A,Smuga-Otto K.et al.2007.Induced pluripotent stem cell lines derived from human somatic cells[J].Science,318(5858):1917-1920.
Zheng K,Wu X,Kaestner K H,et al.2009.The pluripotency factor LIN28 marks undifferentiated spermatogonia in mouse[J].BMC Developmental Biology,9:38.
Zhou J,Ng S B,Chng W J.2013.LIN28/LIN28B:An emerging oncogenic driver in cancer stem cells[J].International Journal of Biochemistry&Cell Biology,45(5):973-978.
Zhu H,Shah S,Shyh-Chang N,et al.2010.Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies[J].Nature Genetics,42(7):626-630.
Ambros V A.1989.A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C.elegans[J].Cell,57(1):49-57.
Assou S,Cerecedo D,Tondeur S,et al.2009.A gene expression signature shared by human mature oocytes and embryonic stem cells[J].BMC Genomics,10(1):10.
Cao D,Allan R W,Cheng L,et al.2011.RNA-binding protein LIN28 is a marker for testicular germ cell tumors[J].Human Pathology,42(5):710-718.
Chatterji P,Rustgi A K.2018.RNA binding proteins in intestinal epithelial biology and colorectal cancer[J].Trends in Molecular Medicine,24(5):490-506.
Childs A J,Kinnell H L,He J,et al.2012.LIN28 is selectively expressed by primordial and pre-meiotic germ cells in the human fetal ovary[J].Stem Cells and Development,21(13):2343-2349.
Corre C,Shinoda G,Zhu H,et al.2016.Sex-specific regulation of weight and puberty by the Lin28/let-7 axis[J].Journal of Endocrinology,228(3):179-191.
El-Khairi R,Parnaik R,Duncan A J,et al.2012.Analysis of LIN28A in early human ovary development and as a candidate gene for primary ovarian insufficiency[J].Molecular and Cellular Endocrinology,351(2):264-268.
Elks C E,Perry J R,Sulem P,et al.2010.Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies[J].Nature Genetics,42(12):1077-1087.
Faas L,Warrander F C,Maguire R,et al.2013.Lin28 proteins are required for germ layer specification in Xenopus[J].Development,140(5):976-986.
Farzaneh M,Attari F,Khoshnam S E.2017.Concise review:LIN28/let-7 signaling,a critical double-negative feedback loop during pluripotency,reprogramming,and tumorigenicity[J].Cell Reprogram,19(5):289-293.
Gaytan F,Sangiao-Alvarellos S,Manfredi-Lozano M,et al.2013.Distinct expression patterns predict differential roles of the miRNA-binding proteins,Lin28 and Lin28b,in the mouse testis:Studies during postnatal development and in a model of hypogonadotropic hypogonadism[J].Endocrinology,154(3):1321-1336.
Gillis A J,Stoop H,Biermann K,et al.2011.Expression and interdependencies of pluripotency factors LIN28,OCT3/4,NANOG and SOX2 in human testicular germ cells and tumours of the testis[J].International Journal of Andrology,34(4 pt 2):e160-e174.
Grieco A,Rzeczkowska P,Alm C,et al.2013.Investigation of peripubertal expression of Lin28a and Lin28b in C57BL/6 female mice[J].Molecular and Cellular Endocrinology,365(2):241-248.
Guo Y,Chen Y,Ito H,et al.2006.Identification and characterization of lin-28 homolog B(LIN28B)in human hepatocellular carcinoma[J].Gene,384(24):51-61.
Hanna J,Saha K,Pando B,et al.2009.Direct cell reprogramming is a stochastic process amenable to acceleration[J].Nature,462(7273):595-601.
He C,Kraft P,Chen C,et al.2009.Genome-wide association studies identify loci associated with age at menarche and age at natural menopause[J].Nature Genetics,41(6):724-728.
Hu Z,Chen R,Cai C.2016.Association of genetic polymorphisms around the LIN28B gene and idiopathic central precocious puberty risks among Chinese girls[J].Pediatric Research,80(4):521-525.
Lee W Y,Park H J,Lee R,et al.2017.Analysis of putative biomarkers of undifferentiated spermatogonia in dog testis[J].Animal Reproduction Science,185:174-180.
Lettre G,Jackson A U,Gieger C,et al.2008.Identification of ten loci associated with height highlights new biological pathways in human growth[J].Nature Genetics,40(5):584-591.
M?kel?J A,Toppari J,Riveromüller A,et al.2014.Reconstruction of mouse testicular cellular microenvironments in long-term seminiferous tubule culture[J].PLoS One,9(3):e90088.
Martins S,Bohndorf M,Schr?ter F,et al.2017.Lymphob last-derived integration-free ISRM-CON9 iPS cell line from a 75 year old female[J].Stem Cell Research,26:76-79.
Matzuk M M.2009.LIN28 lets BLIMP1 take the right course[J].Developmental Cell,17(2):160-161.
Moss E G,Lee R C,Ambros V.1997.The cold shock domain protein LIN28 controls developmental timing in C.elegans and is regulated by the lin-4 RNA[J].Cell,88(5):637-646.
Moss E G,Tang L.2003.Conservation of the heterochronic regulator Lin-28,its developmental expression and microRNA complementary sites[J].Developmental Biology,258(2):432-442.
Murray M J,Saini H K,Siegler C A,et al.2013.LIN28 Expression in malignant germ cell tumors downregulates let-7 and increases oncogene levels[J].Cancer Research,73(15):4872-4884.
Ong K K,Elks C E,Li S,et al.2009.Genetic variation in LIN28B is associated with the timing of puberty[J].Nature Genetics,41(6):729-733.
Ouchi Y,Yamamoto J,Iwamoto T.2014.The heterochronic genes lin-28a and lin-28b play an essential and evolutionarily conserved role in early zebrafish development[J].PLoS One,9(2):e88086.
Park G T,Seo Y M,Lee S Y,et al.2012.Lin28 regulates the expression of neuropeptide Y receptors and oocyte-specific homeobox genes in mouse embryonic stem cells[J].Clinical and Experimental Reproductive Medicine,39(2):87-93.
Perry J R B,Stolk L,Franceschini N,et al.2009.Meta-analysis of genome-wide association data identifies two loci influencing age at menarche[J].Nature Genetics,41(6):648-650.
Sangiao-Alvarellos S,Manfredi-Lozano M,Ruiz-Pino F,et al.2013.Changes in hypothalamic expression of the Lin28/let-7 system and related microRNAs during postnatal maturation and after experimental manipulations of puberty[J].Endocrinology,154(2):942-955.
Sangiao-Alvarellos S,Manfredi-Lozano M,Ruiz-Pino F,et al.2015.Testicular expression of the Lin28/let-7 system:Hormonal regulation and changes during postnatal maturation and after manipulations of puberty[J].Scientific Reports,5:15683.
Shinoda G,Shyh-Chang N,de Soysa T,et al.2013.Fetal deficiency of lin28 programs life-long aberrations in growth and glucose metabolism[J].Stem Cells,31(8):1563-1573.
Silveira-neto A P,Leal L F,Emerman A B,et al.2012.Absence of functional LIN28B futations in a large cohort of patients with idiopathic central precocious puberty[J].Hormone Research in Paediatrics,78(3):144-150.
Srivastava V K,Hiney J K,Stevener K,et al.2015.Differential effects of alcohol on excitatory and inhibitory puberty-related peptides in the basal hypothalamus of the female rat[J].Alcoholism:Clinical and Experimental Research,39(12):2386-2393.
Stratoulias V,Heino T I,Michon F.2014.Lin-28 regulates oogenesis and muscle formation in Drosophila melanogaster[J].PLOS One,9(6):e101141.
Sulem P,Gudbjartsson D F,Rafnar T,et al.2009.Genomewide association study identifies sequence variants on6q21 associated with age at menarche[J].Nature Genetics,41(6):734-738.
Thornton J E,Gregory R I.2012.How does Lin28 let-7 control development and disease?[J]Trends in Cell Biology,22(9):474-482.
Tommiska J,S?rensen K,Aksglaede L,et al.2011.LIN28B,LIN28A,KISS1,and KISS1R in idiopathic central precocious puberty[J].BMC Research Notes,4(1):363-363.
Urbach A,Yermalovich A,Zhang J,et al.2014.Lin28 sustains early renal progenitors and induces Wilms tumor[J].Genes&Development,28(9):971-982.
Virant-Klun I,Skutella T,Stimpfel M,et al.2011.Ovarian surface epithelium in patients with severe ovarian infertility:A potential source of cells expressing markers of pluripotent/multipotent stem cells[J].Journal of Biomedicine and Biotechnology,2011:381928.
Viswanathan S R,Powers J T,Einhorn W,et al.2009.Lin28promotes transformation and is associated with advanced human malignancies[J].Nature Genetics,41(7):843-848.
Voutsadakis I A.2018.The pluripotency network in colorectal cancer pathogenesis and prognosis:An update[J].Biomarkers in Medicine,12(6):653-665.
Widén E,Ripatti S,Cousminer D L,et al.2010.Distinct variants at LIN28B influence growth in height from birth to adulthood[J].The American Journal of Human Genetics,86(5):773-782.
West J A,Viswanathan S R,Yabuuchi A,et al.2009.A role for Lin28 in primordial germ-cell development and germ-cell malignancy[J].Nature,460(7257):909-914.
Werler S,Demond H,Damm O S,et al.2014.Germ cell loss is associated with fading Lin28a expression in a mouse model for Klinefelter's syndrome[J].Reproduction,147(3):253-264
Yang D H,Moss E G.2003.Temporally regulated expression of Lin-28 in diverse tissues of the developing mouse[J].Gene Expression Pattern,3(6):719-726.
Yang M,Yang S L,Herrlinger S,et al.2015.Lin28 promotes the proliferative capacity of neural progenitor cells in brain development[J].Development,142(9):1616-1627.
Yu J,Vodyanik M A,Smuga-Otto K.et al.2007.Induced pluripotent stem cell lines derived from human somatic cells[J].Science,318(5858):1917-1920.
Zheng K,Wu X,Kaestner K H,et al.2009.The pluripotency factor LIN28 marks undifferentiated spermatogonia in mouse[J].BMC Developmental Biology,9:38.
Zhou J,Ng S B,Chng W J.2013.LIN28/LIN28B:An emerging oncogenic driver in cancer stem cells[J].International Journal of Biochemistry&Cell Biology,45(5):973-978.
Zhu H,Shah S,Shyh-Chang N,et al.2010.Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies[J].Nature Genetics,42(7):626-630.