• PMID: 23640459
• Gene Name: MIR383
• Condition: Contributes to human spermatogenic failure with Maturation arrest
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Contributes to human spermatogenic failure with Maturation arrest

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

Tian H, Cao YX, Zhang XS, Liao WP, Yi YH, Lian J, Liu L, Huang HL, Liu WJ, Yin MM, Liang M, Shan G, Sun F.

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. FAU - Tian, H AU - Tian H AD - Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China. FAU - Cao, Y-X AU - Cao YX FAU - Zhang, X-S AU - Zhang XS FAU - Liao, W-P AU - Liao WP FAU - Yi, Y-H AU - Yi YH FAU - Lian, J AU - Lian J FAU - Liu, L AU - Liu L FAU - Huang, H-L AU - Huang HL FAU - Liu, W-J AU - Liu WJ FAU - Yin, M-M AU - Yin MM FAU - Liang, M AU - Liang M FAU - Shan, G AU - Shan G