Primary biliary cirrhosis is associated with altered hepatic microRNA expression

Kerstien A. Padgett, Ruth Y. Lan, Patrick S Leung, Ana Lleo, Kevin Dawson, Janice Pfeiff, Tin K. Mao, Ross L. Coppel, Aftab A. Ansari, M. Eric Gershwin

Research output: Contribution to journalArticle

158 Scopus citations

Abstract

MicroRNAs (miRNAs) are small RNA molecules that negatively regulate protein coding gene expression and are thought to play a critical role in many biological processes. Aberrant levels of miRNAs have been associated with numerous diseases and cancers, and as such, miRNAs have gain much interests as diagnostic biomarkers, and as therapeutic targets. However, their role in autoimmunity is largely unknown. The aims of this study are to: (1) identify differentially expressed miRNAs in human primary biliary cirrhosis (PBC); (2) validate these independently; and (3) identify potential targets of differentially expressed miRNAs. We compared the expression of 377 miRNAs in explanted livers form subjects with PBC versus controls with normal liver histology. A total of 35 independent miRNAs were found to be differentially expressed in PBC (p < 0.001). Quantitative PCR was employed to validate down-regulation of microRNA-122a (miR-122a) and miR-26a and the increased expression of miR-328 and miR-299-5p. The predicted targets of these miRNAs are known to affect cell proliferation, apoptosis, inflammation, oxidative stress, and metabolism. Our data are the first to demonstrate that PBC is characterized by altered expression of hepatic miRNA; however additional studies are required to demonstrate a causal link between those miRNA and the development of PBC.

Original languageEnglish (US)
Pages (from-to)246-253
Number of pages8
JournalJournal of Autoimmunity
Volume32
Issue number3-4
DOIs
StatePublished - May 2009

Keywords

  • Autoimmune liver diseases
  • MicroRNA
  • Primary biliary cirrhosis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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    Padgett, K. A., Lan, R. Y., Leung, P. S., Lleo, A., Dawson, K., Pfeiff, J., Mao, T. K., Coppel, R. L., Ansari, A. A., & Gershwin, M. E. (2009). Primary biliary cirrhosis is associated with altered hepatic microRNA expression. Journal of Autoimmunity, 32(3-4), 246-253. https://doi.org/10.1016/j.jaut.2009.02.022