MicroRNA-19a mediates the suppressive effect of laminar flow on cyclin D1 expression in human umbilical vein endothelial cells

Xiaomei Qin, Xiaohong Wang, Ying Wang, Zhihui Tang, Qinghua Cui, Jianzhong Xi, Yi Shuan J. Li, Shu Chien, Nanping Wang

Research output: Contribution to journalArticlepeer-review

174 Scopus citations

Abstract

Endothelial cells (ECs) respond to changes in mechanical forces, leading to the modulation of signaling networks and cell function; an example is the inhibition of EC proliferation by steady laminar flow. MicroRNAs (miRs) are short noncoding 20-22 nucleotide RNAs that negatively regulate the expression of target genes at the posttranscriptional level. This study demonstrates that miRs are involved in the flow regulation of gene expression in ECs. With the use of microRNA chip array, we found that laminar shear stress (12 dyn/cm 2, 12 h) regulated the EC expression of manymiRs, including miR-19a.Wefurther showed that stable transfection of miR-19a significantly decreased the expression of a reporter gene controlled by a conserved 3′-untranslated region of the cyclinD1 gene and also the protein level of cyclin D1, leading to an arrest of cell cycle at G1/S transition. Laminar flow suppressed cyclin D1 protein level, and this suppressive effect was diminished when the endogenous miR-19a was inhibited. In conclusion, we demonstrated that miR-19a plays an important role in the flow regulation of cyclin D1 expression. These results revealed a mechanism by which mechanical forces modulate endothelial gene expression.

Original languageEnglish (US)
Pages (from-to)3240-3244
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number7
DOIs
StatePublished - Feb 16 2010

Keywords

  • Cell cycle
  • Endothelium
  • Flow
  • Gene expression
  • Noncoding RNA

ASJC Scopus subject areas

  • General

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