miRNA Biogenesis Enzyme Drosha Is Required for Vascular Smooth Muscle Cell Survival

Pei Fan, Zixuan Chen, Peng Tian, Wen Liu, Yan Jiao, Yi Xue, Anindya Bhattacharya, Jianmin Wu, Meifen Lu, Yuqi Guo, Yan Cui, Weikuan Gu, Weiwang Gu, Junming Yue

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

miRNA biogenesis enzyme Drosha cleaves double-stranded primary miRNA by interacting with double-stranded RNA binding protein DGCR8 and processes primary miRNA into precursor miRNA to participate in the miRNA biogenesis pathway. The role of Drosha in vascular smooth muscle cells (VSMCs) has not been well addressed. We generated Drosha conditional knockout (cKO) mice by crossing VSMC-specific Cre mice, SM22-Cre, with Drosha loxp/loxp mice. Disruption of Drosha in VSMCs resulted in embryonic lethality at E14.5 with severe liver hemorrhage in mutant embryos. No obvious developmental delay was observed in Drosha cKO embryos. The vascular structure was absent in the yolk sac of Drosha homozygotes at E14.5. Loss of Drosha reduced VSMC proliferation in vitro and in vivo. The VSMC differentiation marker genes, including αSMA, SM22, and CNN1, and endothelial cell marker CD31 were significantly downregulated in Drosha cKO mice compared to controls. ERK1/2 mitogen-activated protein kinase and the phosphatidylinositol 3-kinase/AKT were attenuated in VSMCs in vitro and in vivo. Disruption of Drosha in VSMCs of mice leads to the dysregulation of miRNA expression. Using bioinformatics approach, the interactions between dysregulated miRNAs and their target genes were analyzed. Our data demonstrated that Drosha is required for VSMC survival by targeting multiple signaling pathways.

Original languageEnglish (US)
Article numbere60888
JournalPLoS ONE
Volume8
Issue number4
DOIs
StatePublished - Apr 18 2013

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MicroRNAs
microRNA
Vascular Smooth Muscle
blood vessels
smooth muscle
myocytes
Smooth Muscle Myocytes
cell viability
Muscle
Cell Survival
Cells
Enzymes
enzymes
mice
Knockout Mice
Embryonic Structures
Genes
embryo (animal)
Phosphatidylinositol 3-Kinase
Yolk Sac

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

miRNA Biogenesis Enzyme Drosha Is Required for Vascular Smooth Muscle Cell Survival. / Fan, Pei; Chen, Zixuan; Tian, Peng; Liu, Wen; Jiao, Yan; Xue, Yi; Bhattacharya, Anindya; Wu, Jianmin; Lu, Meifen; Guo, Yuqi; Cui, Yan; Gu, Weikuan; Gu, Weiwang; Yue, Junming.

In: PLoS ONE, Vol. 8, No. 4, e60888, 18.04.2013.

Research output: Contribution to journalArticle

Fan, P, Chen, Z, Tian, P, Liu, W, Jiao, Y, Xue, Y, Bhattacharya, A, Wu, J, Lu, M, Guo, Y, Cui, Y, Gu, W, Gu, W & Yue, J 2013, 'miRNA Biogenesis Enzyme Drosha Is Required for Vascular Smooth Muscle Cell Survival', PLoS ONE, vol. 8, no. 4, e60888. https://doi.org/10.1371/journal.pone.0060888
Fan, Pei ; Chen, Zixuan ; Tian, Peng ; Liu, Wen ; Jiao, Yan ; Xue, Yi ; Bhattacharya, Anindya ; Wu, Jianmin ; Lu, Meifen ; Guo, Yuqi ; Cui, Yan ; Gu, Weikuan ; Gu, Weiwang ; Yue, Junming. / miRNA Biogenesis Enzyme Drosha Is Required for Vascular Smooth Muscle Cell Survival. In: PLoS ONE. 2013 ; Vol. 8, No. 4.
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