The targeting and functions of miRNA-383 are mediated by FMRP during spermatogenesis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-05

AUTHORS

H Tian, Y-X Cao, X-S Zhang, W-P Liao, Y-H Yi, J Lian, L Liu, H-L Huang, W-J Liu, M-M Yin, M Liang, G Shan, F Sun

ABSTRACT

Our previous studies have shown that microRNA-383 (miR-383) expression is downregulated in the testes of infertile men with maturation arrest (MA). Abnormal testicular miR-383 expression may potentiate the connections between male infertility and testicular germ cell tumors. However, the mechanisms underlying the targeting and functions of miR-383 during spermatogenesis remain unknown. In this study, we found that fragile X mental retardation protein (FMRP) was associated with 88 miRNAs in mouse testis including miR-383. Knockdown of FMRP in NTERA-2 (NT2) (testicular embryonal carcinoma) cells enhanced miR-383-induced suppression of cell proliferation by decreasing the interaction between FMRP and miR-383, and then affecting miR-383 binding to the 3'-untranslated region of its target genes, including interferon regulatory factor-1 (IRF1) and Cyclin D1 both in vivo and in vitro. On the other hand, FMRP levels were also downregulated by overexpression of miR-383 in NT2 cells and GC1 (spermatogonia germ cell line). miR-383 targeted to Cyclin D1 directly, and then inhibited its downstream effectors, including phosphorylated pRb and E2F1, which ultimately resulted in decreased FMRP expression. Reduced miR-383 expression, dysregulated cyclin-dependent kinase 4 expression (one of the downstream genes of miR-383) and increased DNA damage were also observed in the testes of Fmr1 knockout mice and of MA patients with a downregulation of FMRP. A potential feedback loop between FMRP and miR-383 during spermatogenesis is proposed, and FMRP acts as a negative regulator of miR-383 functions. Our data also indicate that dysregulation of the FMRP-miR-383 pathway may partially contribute to human spermatogenic failure with MA. More... »

PAGES

e617

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/cddis.2013.138

DOI

http://dx.doi.org/10.1038/cddis.2013.138

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1034562943

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23640459


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