A Micro RNA Processing Defect in Rapidly Progressing Idiopathic Pulmonary Fibrosis

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Jun 30

PMID 21712985

Citations 73

Authors

Sameer R Oak

Lynne Murray

Athula Herath

Matthew Sleeman

Ian Anderson

Amrita D Joshi

Ana Lucia Coelho

Kevin R Flaherty

Galen B Toews

Darryl Knight

Fernando J Martinez

Cory M Hogaboam

Affiliations

Soon will be listed here.

Abstract

Background: Idiopathic pulmonary fibrosis exhibits differential progression from the time of diagnosis but the molecular basis for varying progression rates is poorly understood. The aim of the present study was to ascertain whether differential miRNA expression might provide one explanation for rapidly versus slowly progressing forms of IPF.

Methodology And Principal Findings: miRNA and mRNA were isolated from surgical lung biopsies from IPF patients with a clinically documented rapid or slow course of disease over the first year after diagnosis. A quantitative PCR miRNA array containing 88 of the most abundant miRNA in the human genome was used to profile lung biopsies from 9 patients with rapidly progressing IPF, 6 patients with slowly progressing IPF, and 10 normal lung biopsies. Using this approach, 11 miRNA were significantly increased and 36 were significantly decreased in rapid biopsies compared with normal biopsies. Slowly progressive biopsies exhibited 4 significantly increased miRNA and 36 significantly decreased miRNA compared with normal lung. Among the miRNA present in IPF with validated mRNA targets were those with regulatory effects on epithelial-mesenchymal transition (EMT). Five miRNA (miR-302c, miR-423-5p, miR-210, miR-376c, and miR-185) were significantly increased in rapid compared with slow IPF lung biopsies. Additional analyses of rapid biopsies and fibroblasts grown from the same biopsies revealed that the expression of AGO1 and AGO2 (essential components of the miRNA processing RISC complex) were lower compared with either slow or normal lung biopsies and fibroblasts.

Conclusion: These findings suggest that the development and/or clinical progression of IPF might be the consequence of aberrant miRNA processing.

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References

Lim L, Lau N, Garrett-Engele P, Grimson A, Schelter J, Castle J . Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005; 433(7027):769-73. DOI: 10.1038/nature03315. View

Boon K, Bailey N, Yang J, Steel M, Groshong S, Kervitsky D . Molecular phenotypes distinguish patients with relatively stable from progressive idiopathic pulmonary fibrosis (IPF). PLoS One. 2009; 4(4):e5134. PMC: 2661376. DOI: 10.1371/journal.pone.0005134. View

Karube Y, Tanaka H, Osada H, Tomida S, Tatematsu Y, Yanagisawa K . Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Sci. 2005; 96(2):111-5. PMC: 11158408. DOI: 10.1111/j.1349-7006.2005.00015.x. View

Oglesby I, Bray I, Chotirmall S, Stallings R, ONeill S, McElvaney N . miR-126 is downregulated in cystic fibrosis airway epithelial cells and regulates TOM1 expression. J Immunol. 2010; 184(4):1702-9. DOI: 10.4049/jimmunol.0902669. View

Guo C, Pan Q, Cheng T, Jiang B, Chen G, Li D . Changes in microRNAs associated with hepatic stellate cell activation status identify signaling pathways. FEBS J. 2009; 276(18):5163-76. DOI: 10.1111/j.1742-4658.2009.07213.x. View

Kim D, Collard H, King Jr T . Classification and natural history of the idiopathic interstitial pneumonias. Proc Am Thorac Soc. 2006; 3(4):285-92. PMC: 2658683. DOI: 10.1513/pats.200601-005TK. View

Selman M, Carrillo G, Estrada A, Mejia M, Becerril C, Cisneros J . Accelerated variant of idiopathic pulmonary fibrosis: clinical behavior and gene expression pattern. PLoS One. 2007; 2(5):e482. PMC: 1868965. DOI: 10.1371/journal.pone.0000482. View

Duisters R, Tijsen A, Schroen B, Leenders J, Lentink V, van der Made I . miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circ Res. 2008; 104(2):170-8, 6p following 178. DOI: 10.1161/CIRCRESAHA.108.182535. View

Dutsch-Wicherek M . RCAS1, MT, and vimentin as potential markers of tumor microenvironment remodeling. Am J Reprod Immunol. 2010; 63(3):181-8. DOI: 10.1111/j.1600-0897.2009.00803.x. View

10.

Cowland J, Hother C, Gronbaek K . MicroRNAs and cancer. APMIS. 2007; 115(10):1090-106. DOI: 10.1111/j.1600-0463.2007.apm_775.xml.x. View

11.

Yokoyama A, Kohno N, Hamada H, Sakatani M, Ueda E, Kondo K . Circulating KL-6 predicts the outcome of rapidly progressive idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1998; 158(5 Pt 1):1680-4. DOI: 10.1164/ajrccm.158.5.9803115. View

12.

Ji J, Zhang J, Huang G, Qian J, Wang X, Mei S . Over-expressed microRNA-27a and 27b influence fat accumulation and cell proliferation during rat hepatic stellate cell activation. FEBS Lett. 2009; 583(4):759-66. DOI: 10.1016/j.febslet.2009.01.034. View

13.

Jiang X, Tsitsiou E, Herrick S, Lindsay M . MicroRNAs and the regulation of fibrosis. FEBS J. 2010; 277(9):2015-21. PMC: 2963651. DOI: 10.1111/j.1742-4658.2010.07632.x. View

14.

Liu G, Friggeri A, Yang Y, Milosevic J, Ding Q, Thannickal V . miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis. J Exp Med. 2010; 207(8):1589-97. PMC: 2916139. DOI: 10.1084/jem.20100035. View

15.

Van Rooij E, Olson E . Searching for miR-acles in cardiac fibrosis. Circ Res. 2009; 104(2):138-40. PMC: 2747251. DOI: 10.1161/CIRCRESAHA.108.192492. View

16.

Grimson A, Farh K, Johnston W, Garrett-Engele P, Lim L, Bartel D . MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell. 2007; 27(1):91-105. PMC: 3800283. DOI: 10.1016/j.molcel.2007.06.017. View

17.

Frankel S, Schwarz M . Update in idiopathic pulmonary fibrosis. Curr Opin Pulm Med. 2009; 15(5):463-9. DOI: 10.1097/MCP.0b013e32832ea4b3. View

18.

Willis B, Borok Z . TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease. Am J Physiol Lung Cell Mol Physiol. 2007; 293(3):L525-34. DOI: 10.1152/ajplung.00163.2007. View

19.

Guo H, Ingolia N, Weissman J, Bartel D . Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010; 466(7308):835-40. PMC: 2990499. DOI: 10.1038/nature09267. View

20.

Kumar M, Lu J, Mercer K, Golub T, Jacks T . Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet. 2007; 39(5):673-7. DOI: 10.1038/ng2003. View