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MiR-30c-1-3p targets matrix metalloproteinase 9 involved in the rupture of abdominal aortic aneurysms.

Abstract
Abdominal aortic aneurysm (AAA) can be fatal if ruptured, but there is no predictive biomarker. Our aim was to evaluate the prognostic potential of microRNAs (miRNAs/miRs) in an AAA mouse model and patients with unruptured AAA (URAAA) and ruptured AAA (RAAA). Among the 64 miRNAs differentially expressed in mice with AAA compared to control, miR-30c-1-3p, miR-432-3p, miR-3154, and miR-379-5p had high homology with human miRNAs. MiR-30c-1-3p plasma levels were significantly lower in patients with RAAA than in those with URAAA or control and tended to negatively correlate with the maximum aortic diameter (r =  -0.3153, P = 0.06109). MiR-30c-1-3p targeted matrix metalloproteinase (MMP)-9 mRNA through the coding region and downregulated its expression in vitro. MMP-9 plasma concentrations were significantly higher in the RAAA group than in the URAAA group (P < 0.001) and were negatively associated with miR-30c-1-3p levels (r =  -0.3671, P = 0.01981) and positively-with the maximal aortic diameter (r = 0.6251, P < 0.0001). The optimal cutoff values for MMP-9 expression and the maximal aortic diameter were 461.08 ng/ml and 55.95 mm, with areas under the curve of 0.816 and 0.844, respectively. Our results indicate that plasma levels of miR-30c-1-3p and MMP-9 may be candidate biomarkers of AAA progression. KEY MESSAGES: Downregulation of miR-30c-1-3p expression and upregulation of its potential target MMP-9 are predictors of the devastation of AAA. Downregulation of miR-30c-1-3p expression and its downstream impact on MMP-9 have a potential on predicting the development and rupture of AAA.
AuthorsLin Yang, Hong-Gang Sui, Meng-Meng Wang, Jia-Yin Li, Xiao-Feng He, Jing-Yuan Li, Xiao-Zeng Wang
JournalJournal of molecular medicine (Berlin, Germany) (J Mol Med (Berl)) Vol. 100 Issue 8 Pg. 1209-1221 (08 2022) ISSN: 1432-1440 [Electronic] Germany
PMID35840740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2022. The Author(s).
Chemical References
  • Biomarkers
  • MicroRNAs
  • Matrix Metalloproteinase 9
Topics
  • Animals
  • Aortic Aneurysm, Abdominal (genetics)
  • Biomarkers
  • Down-Regulation
  • Humans
  • Matrix Metalloproteinase 9 (genetics, metabolism)
  • Mice
  • MicroRNAs (metabolism)
  • Up-Regulation

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