Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth

Kuei Chun Wang, Lana Xia Garmire, Angela Young, Phu Nguyen, Andrew Trinh, Shankar Subramaniam, Nanping Wang, John Y.J. Shyy, Yi Shuan Li, Shu Chien

Research output: Contribution to journalArticlepeer-review

139 Scopus citations

Abstract

MicroRNAs (miRs) can regulate many cellular functions, but their roles in regulating responses of vascular endothelial cells (ECs) to mechanical stimuli remain unexplored. We hypothesize that the physiological responses of ECs are regulated by not only mRNA and protein signaling networks, but also expression of the corresponding miRs. EC growth arrest induced by pulsatile shear (PS) flow is an important feature for flowregulation of ECs. miR profiling showed that 21 miRs are differentially expressed(8up- and 13downregulated) inresponse to 24-h PS as compared to static condition (ST). The mRNA expression profile indicates EC growth arrest under 24-h PS. Analysis of differentially expressed miRs yielded 68 predicted mRNA targets that overlapped with results of microarray mRNA profiling. Functional analysis of miR profile indicates that the cell cycle network is highly regulated. The upregulation of miR-23b and miR-27b was found to correlatewith the PS-induced EC growth arrest. Inhibition of miR-23b using antagomir-23b oligonucleotide (AM23b) reversed the PS-induced E2F1 reduction and retinoblastoma (Rb) hypophosphorylation and attenuated the PS-induced G1/G0 arrest. Antagomir AM27b regulated E2F1 expression, but did not affect Rb and growth arrest. Our findings indicate that PS suppresses EC proliferation through the regulation of miR-23b and provide insights into the role of miRs in mechanotransduction.

Original languageEnglish (US)
Pages (from-to)3234-3239
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number7
DOIs
StatePublished - Feb 16 2010
Externally publishedYes

Keywords

  • Bioinformatics
  • Cell cycle
  • Gene regulation
  • Mechanotransduction
  • Shear

ASJC Scopus subject areas

  • General

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