miR-18, a member of Oncomir-1, targets heat shock transcription factor 2 in spermatogenesis

Abstract

SUMMARYmiR-18 belongs to the Oncomir-1 or miR-17~92 cluster that is intimately associated with the occurrence and progression of different types of cancer. However, the physiological roles of the Oncomir-1 cluster and its individual miRNAs are largely unknown. Here, we describe a novel function for miR-18 in mouse. We show that miR-18 directly targets heat shock factor 2 (HSF2), a transcription factor that influences a wide range of developmental processes including embryogenesis and gametogenesis. Furthermore, we show that miR-18 is highly abundant in testis, displaying distinct cell-type-specific expression during the epithelial cycle that constitutes spermatogenesis. Expression of HSF2 and of miR-18 exhibit an inverse correlation during spermatogenesis, indicating that, in germ cells, HSF2 is downregulated by miR-18. To investigate the in vivo function of miR-18 we developed a novel method, T-GIST, and demonstrate that inhibition of miR-18 in intact seminiferous tubules leads to increased HSF2 protein levels and altered expression of HSF2 target genes. Our results reveal that miR-18 regulates HSF2 activity in spermatogenesis and link miR-18 to HSF2-mediated physiological processes such as male germ cell maturation.

MicroRNAs and DNA methylation as epigenetic regulators of mitosis, meiosis and spermiogenesis

“…MiR-18 is abundantly expressed in the testis and it displays cell type-specific expression, with the highest intensity in spermatocytes. Meanwhile, miR-18 directly targets heat R28 C Yao, Y Liu and others shock factor 2, which is a key transcription factor essential for influencing embryogenesis and gametogenesis (Bjork et al 2010).…”

A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART)

“…Other recent reports have also highlighted the importance of miR-18 in the control of heat shock factor 2, a transcription factor that is required for normal spermatogenesis in mouse [182]. miR-34c and miRNA34b are important players in the later steps of spermatogenesis in germ cells [233] and differentiation of male germ cells [183].…”

Chromatoid body and small RNAs in male germ cells

“…Some examples of miRNAmediated regulation of gene expression in spermatogenesis exist, such as the control of heat shock factor 2, a transcription factor that is required for normal spermatogenesis in mouse, by miR-18 (Bjork et al 2010) and the involvement of miR-17-92 cluster in the regulation of E2F-1 transcription factor during normal spermatogenesis and in carcinoma in situ (Novotny et al 2007). The impact of DICER-dependent small RNA pathways in male fertility has begun to be revealed by studies on different genetically modified mouse lines.…”