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

Johanna Björk, A Sandqvist, Alexandra Elsing, N Kotaja, Lea Sistonen

    Research output: Contribution to journalArticleScientificpeer-review

    85 Citations (Scopus)

    Abstract

    miR-18 belongs to the Oncomir-1 or miR-17 similar to 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.
    Original languageUndefined/Unknown
    Pages (from-to)3177–3184
    Number of pages8
    JournalDevelopment
    Volume137
    Issue number19
    DOIs
    Publication statusPublished - 2010
    MoE publication typeA1 Journal article-refereed

    Keywords

    • HSF
    • microRNA
    • miR-17 similar to 92
    • Mouse
    • Speer4a
    • Ssty2
    • T-GIST

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