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

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Björk JK, Sandqvist A, Elsing AN, Kotaja N, Sistonen L
Förläggare: COMPANY OF BIOLOGISTS LTD
Publiceringsår: 2010
Tidskrift: Development
Tidskriftsakronym: DEVELOPMENT
Volym: 137
Nummer: 19
Artikelns första sida, sidnummer: 3177
Artikelns sista sida, sidnummer: 3184
Antal sidor: 8
ISSN: 0950-1991
eISSN: 1477-9129


Abstrakt

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.


Nyckelord

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

Senast uppdaterad 2019-19-09 vid 05:19