Reduction of microRNA-206 contributes to the development of bronchopulmonary dysplasia through up-regulation of fibronectin 1

PLoS One. 2013 Sep 10;8(9):e74750. doi: 10.1371/journal.pone.0074750. eCollection 2013.

Abstract

Objective: To characterize microRNA-206 (miR-206) in the development of bronchopulmonary dysplasia (BPD).

Design/methods: We assessed the expression of miR-206 in BPD mouse lung tissues and blood samples of BPD patients by quantitative real-time PCR. Then, the role of miR-206 in regulating cell biology were examined by XTT assay, flow cytometry, transwell invasion assay, wound healing assay and adhesion assay in vitro. Furthermore, luciferase reporter assay, real-time PCR, western blot and Immunofluorescence staining were performed to figure out the target gene of miR-206.

Results: A reduction in expression of miR-206 was observed in BPD mice compared with controls and in BPD patients compared with controls. miR-206 overexpression significantly induced cell apoptosis, reduced cell proliferation, migration and adhesion abilities, whereas the inhibition of miR-206 expression had the opposite effect. Fibronectin 1 (FN1) is a direct target of miR-206, and fn 1 can be transcriptionally and translationally regulated by miR-206. Down-regulation of miR-206 modulates biological functions of the cells, at least in part, by increasing the level of fn 1. Furthermore, fn 1 expression levels were increased in the BPD mice and BPD patients.

Conclusions: The expression of miR-206 and its target gene, fn 1, may contribute to the progression of BPD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchopulmonary Dysplasia / genetics*
  • Bronchopulmonary Dysplasia / metabolism*
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Fibronectins / metabolism*
  • Gene Expression Regulation*
  • Humans
  • Lung / metabolism
  • Male
  • Mice
  • MicroRNAs / metabolism*
  • RNA, Small Interfering / metabolism
  • Wound Healing

Substances

  • FN1 protein, human
  • Fibronectins
  • MIRN206 microRNA, human
  • MicroRNAs
  • Mirn206 microRNA, mouse
  • RNA, Small Interfering

Grants and funding

This study was funded by the National Natural Science Foundation of China (81170602, 81270059, 81000265)(https://isis.nsfc.gov.cn; Postdoctoral Science Foundation of China (2012T50889) http://210.79.234.200/V1/Manage/Login.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.