title: Circulating Extracellular RNA Markers of Liver Regeneration.
abstract: OBJECTIVE
  Although a key determinant of hepatic recovery after injury is active liver regeneration, the ability to detect ongoing regeneration is lacking. The restoration of liver mass after hepatectomy involves systemic changes with coordinated changes in gene expression guiding regenerative responses, activation of progenitor cells, and proliferation of quiescent hepatocytes. We postulated that these responses involve intercellular communication involving extracellular RNA and that these could represent biomarkers of active regenerative responses.
  
  
  METHODS
  RNA sequencing was performed to identify temporal changes in serum extracellular non-coding RNA after partial hepatectomy in C57BL/6 male mice. Tissue expression of selected RNA was performed by microarray analysis and validated using qRT-PCR. Digital PCR was used to detect and quantify serum expression of selected RNA.
  
  
  RESULTS
  A peak increase in extracellular RNA content occurred six hours after hepatectomy. RNA sequencing identified alterations in several small non-coding RNA including known and novel microRNAs, snoRNAs, tRNA, antisense and repeat elements after partial hepatectomy. Combinatorial effects and network analyses identified signal regulation, protein complex assembly, and signal transduction as the most common biological processes targeted by miRNA that altered. miR-1A and miR-181 were most significantly altered microRNA in both serum and in hepatic tissues, and their presence in serum was quantitated using digital PCR.
  
  
  CONCLUSIONS
  Extracellular RNA selectively enriched during acute regeneration can be detected within serum and represent biomarkers of ongoing liver regeneration in mice. The ability to detect ongoing active regeneration would improve the assessment of hepatic recovery from liver injury.
authors.affiliation: Department of Transplantation, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL 32224, United States of America.|Department of Cancer Biology, 4500 San Pablo Road South, Jacksonville, FL 32224, United States of America.
authors.forename: Irene K
authors.initials: IK
authors.lastname: Yan
authors.affiliation: Department of Health Sciences Research, 4500 San Pablo Road South, Jacksonville, FL 32224, United States of America.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Health Sciences Research, 4500 San Pablo Road South, Jacksonville, FL 32224, United States of America.
authors.forename: Yan W
authors.initials: YW
authors.lastname: Asmann
authors.affiliation: Department of Transplantation, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL 32224, United States of America.|Department of Cancer Biology, 4500 San Pablo Road South, Jacksonville, FL 32224, United States of America.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Haga
authors.affiliation: Department of Transplantation, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL 32224, United States of America.|Department of Cancer Biology, 4500 San Pablo Road South, Jacksonville, FL 32224, United States of America.
authors.forename: Tushar
authors.initials: T
authors.lastname: Patel
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D006498:Hepatectomy; D008099:Liver / Q000378:metabolism*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058727:RNA, Small Untranslated / Q000097:blood*; D013997:Time Factors; D046888:Tissue Array Analysis
chemical_list: D015415:Biomarkers; D058727:RNA, Small Untranslated