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- W27458787 abstract "Gonadotropin-releasing hormone (GnRH) plays a vital role in the mammal reproductive system by regulating biosynthesis in the pituitary gonadotrope via a complex signaling pathway and gene network. Small non-coding microRNAs (miRNA) are found to play important roles in post-transcriptional gene regulation of many genes. Previously, it has been shown that tonic GnRH treatment of L[Beta]T2 cells causes cell cycle arrest, leading to subsequent apoptosis. Here, we investigated whether miRNA- 132/212, the microRNAs most induced upon GnRH stimulation, mediate the anti-proliferative effect of GnRH on these cells. GnRH treatment for increasing times causes increase in both the transcript and mature forms of miR-132/212 levels as measured by qPCR. This miR-132/212 expression were abolished by pretreatment with the adenylate cyclase inhibitor SQ 22536 and MEK inhibitor U0126. SirT-1 was identified as a putative target of miR-132/212 by miRANDA, TargetScan, and miRacle. Acetylated p53, a substrate of SirT-1 deacetylase, was found to be upregulated as a result of GnRH stimulation. P21, a transcriptional target of p53, was also shown to be upregulated as a result of GnRH treatment. These changes in protein levels and block in cell proliferation were recapitulated by transfection of L[Beta]T2 cells by pre-miR-132/212, as well as blocked by transfection with anti-miR-132/212 prior to GnRH stimulation. Taken together, our data suggest a possible mechanism by which gonadotropes utilize microRNAs to synchronise their response to GnRH leading to coordinated gonadotropin release and the possible role of microRNAs in the global regulation of reproduction" @default.
- W27458787 created "2016-06-24" @default.
- W27458787 creator A5049133729 @default.
- W27458787 date "2011-01-01" @default.
- W27458787 modified "2023-09-26" @default.
- W27458787 title "MicroRNA132/212 mediates the anti-proliferative action of GnRH by downregulation of SirT-1 in pituitary LbetaT2 Gonadotropes" @default.
- W27458787 hasPublicationYear "2011" @default.
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