- 作者: Xiaomin Zhang; Gohar Azhar; Scott A. Helms; Jeanne Y. Wei
- 作者服務機構: Donald W. Reynolds Department of Geriatrics, The University of Arkansas for Medical Sciences and Geriatric Research, Education and Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, AR., U.S.A.
- 中文摘要: --
- 英文摘要:
Serum response factor (SRF) regulates certain microRNAs that play a role in cardiac and
skeletal muscle development. However, the role of SRF in the regulation of microRNA
expression and microRNA biogenesis in cardiac hypertrophy has not been well established. In
this report, we employed two distinct transgenic mouse models to study the impact of SRF on
cardiac microRNA expression and microRNA biogenesis. Cardiac-specific overexpression of
SRF (SRF-Tg) led to altered expression of a number of microRNAs. Interestingly,
downregulation of miR-1, miR-133a and upregulation of miR-21 occurred by 7 days of age in
these mice, long before the onset of cardiac hypertrophy, suggesting that SRF overexpression
impacted the expression of microRNAs which contribute to cardiac hypertrophy. Reducing
cardiac SRF level using the antisense-SRF transgenic approach (Anti-SRF-Tg) resulted in the
expression of miR-1, miR-133a and miR-21 in the opposite direction. Furthermore, we observed
that SRF regulates microRNA biogenesis, specifically the transcription of pri-microRNA,
thereby affecting the mature microRNA level. The mir-21 promoter sequence is conserved
among mouse, rat and human; one SRF binding site was found to be in the mir-21 proximal
promoter region of all three species. The mir-21 gene is regulated by SRF and its cofactors,
including myocardin and p49/Strap. Our study demonstrates that the downregulation of miR-1,
miR-133a, and upregulation of miR-21 can be reversed by one single upstream regulator, SRF.
These results may help to develop novel therapeutic interventions targeting microRNA
biogenesis. - 中文關鍵字: --
- 英文關鍵字: --