Role of miR-34c microRNA in the late steps of spermatogenesis

被引:237
作者
Bouhallier, Frantz [1 ]
Allioli, Nathalie [2 ,3 ]
Lavial, Fabrice [1 ]
Chalmel, Frederic [4 ,5 ]
Perrard, Marie-Helene [1 ]
Durand, Philippe [1 ]
Samarut, Jacques [1 ,2 ,6 ,7 ]
Pain, Bertrand [1 ,8 ]
Rouault, Jean-Pierre [1 ]
机构
[1] Univ Lyon 1, Ecole Normale Super Lyon, IGFL, CNRS,INRA,UMR 5242,UMR1288, F-69364 Lyon 07, France
[2] INRA, CNRS, IGFL, Fac Med,Plateforme CLARA,UMR5242,UMR1288, F-69495 Pierre Benite, France
[3] Univ Lyon 1, ISPB Lyon, F-69622 Villeurbanne, France
[4] Univ Rennes 1, INSERM, GERHM, U625,IFR140, F-35042 Rennes, France
[5] Univ Rennes 1, UMR S625, F-35042 Rennes, France
[6] Univ Lyon 1, Fac Med Lyon Sud, F-69622 Villeurbanne, France
[7] HCL, Ctr Hosp Lyon Sud, UMOMT, F-69495 Pierre Benite, France
[8] Univ Clermont Ferrand 2, INSERM, CNRS, UMR 6247, Clermont Ferrand, France
关键词
miR-34c; spermatogenesis; miRNA; DDX4/VASA; TUMOR-SUPPRESSIVE MIR-34A; DOWN-REGULATION; DIRECT TARGET; TGF-BETA; EXPRESSION; P53; TESTIS; RNA; MICROARRAY; PATHWAY;
D O I
10.1261/rna.1963810
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Spermatogenesis is a cyclic process in which diploid spermatogonia differentiate into haploid spermatozoa. This process is highly regulated, notably at the post-transcriptional level. MicroRNAs (miRNAs), single-stranded noncoding RNA molecules of about 20-25 nucleotides, are implicated in the regulation of many important biological pathways such as proliferation, apoptosis, and differentiation. We wondered whether miRNAs could play a role during spermatogenesis. The miRNA expression repertoire was tested in germ cells, and we present data showing that miR-34c was highly expressed only in these cells. Furthermore, our findings indicate that in male gonads, miR-34c expression is largely p53 independent in contrast to previous results showing a direct link in somatic cells between the miR-34 family and this tumor suppressor protein. In order to identify target genes involved in germinal lineage differentiation, we overexpressed miR-34c in HeLa cells, analyzed the transcriptome of these modified cells, and noticed a shift of the expression profile toward the germinal lineage. Recently, it has been shown that exogenous expression of Ddx4/Vasa in embryonic chicken stem cells (cESC) induces cESC reprogramming toward a germ cell fate. When we simultaneously expressed miR-34c in such cells, we could detect an up-regulation of germ cell-specific genes whereas the expression of other lineage specific markers remained unchanged. These data suggest that miR-34c could play a role by enhancing the germinal phenotype of cells already committed to this lineage.
引用
收藏
页码:720 / 731
页数:12
相关论文
共 72 条
[41]   Full-length hdmX transcripts decrease following genotoxic stress [J].
Markey, M. ;
Berberich, S. J. .
ONCOGENE, 2008, 27 (52) :6657-6666
[42]  
Marret C, 1998, MOL REPROD DEV, V51, P22, DOI 10.1002/(SICI)1098-2795(199809)51:1<22::AID-MRD3>3.0.CO
[43]  
2-Y
[44]   The logic of TGFβ signaling [J].
Massague, Joan ;
Gomis, Roger R. .
FEBS LETTERS, 2006, 580 (12) :2811-2820
[45]   miRGen: a database for the study of animal microRNA genomic organization and function [J].
Megraw, Molly ;
Sethupathy, Praveen ;
Corda, Benoit ;
Hatzigeorgiou, Artemis G. .
NUCLEIC ACIDS RESEARCH, 2007, 35 :D149-D155
[46]   TGIF2 interacts with histone deacetylase I and represses transcription [J].
Melhuish, TA ;
Gallo, CM ;
Wotton, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (34) :32109-32114
[47]   MicroRNAs Impair MET-Mediated Invasive Growth [J].
Migliore, Cristina ;
Petrelli, Annalisa ;
Ghiso, Elena ;
Corso, Simona ;
Capparuccia, Lorena ;
Eramo, Adriana ;
Comoglio, Paolo M. ;
Giordano, Silvia .
CANCER RESEARCH, 2008, 68 (24) :10128-10136
[48]  
Mori S, 2003, DEV GROWTH DIFFER, V45, P7, DOI 10.1046/j.1440-169X.2003.00670.x
[49]   Multiple p53-independent gene silencing mechanisms define the cellular response to p53 activation [J].
Paris, Ramiro ;
Henry, Ryan E. ;
Stephens, Sarah J. ;
McBryde, Meagan ;
Espinosa, Joaquin M. .
CELL CYCLE, 2008, 7 (15) :2427-2433
[50]   β-nerve growth factor participates in an auto/paracrine pathway of regulation of the meiotic differentiation of rat spermatocytes [J].
Perrard, Marie-Helene ;
Vigier, Michele ;
Damestoy, Anne ;
Chapat, Clement ;
Silandre, Dorothee ;
Rudkin, Brian B. ;
Durand, Philippe .
JOURNAL OF CELLULAR PHYSIOLOGY, 2007, 210 (01) :51-62