title: Serum-circulating miRNAs predict neuroblastoma progression in mouse model of high-risk metastatic disease.
abstract: BACKGROUND
  Circulating miRNAs have momentous clinical relevance as prognostic biomarkers and in the progression of solid tumors. Recognizing novel candidates of neuroblastoma-specific circulating miRNAs would allow us to identify potential prognostic biomarkers that could predict the switch from favorable to high-risk metastatic neuroblastoma (HR-NB).
  
  
  RESULTS
  Utilizing mouse models of favorable and HR-NB and whole miRnome profiling, we identified high serum levels of 34 and low levels of 46 miRNAs in animals with HR-NB. Preferential sequence homology exclusion of mouse miRNAs identified 25 (11 increased; 14 decreased) human-specific prognostic marker candidates, of which, 21 were unique to HR-NB. miRNA QPCR validated miRnome profile. Target analysis defined the candidate miRNAs' signal transduction flow-through and demonstrated their converged roles in tumor progression. miRNA silencing studies verified the function of select miRNAs on the translation of at least 14 target proteins. Expressions of critical targets that correlate tumor progression in tissue of multifarious organs identify the orchestration of HR-NB. Significant (>10 fold) increase in serum levels of miR-381, miR-548h, and miR-580 identify them as potential prognostic markers for neuroblastoma progression.
  
  
  CONCLUSIONS
  For the first time, we identified serum-circulating miRNAs that predict the switch from favorable to HR-NB and, further imply that these miRNAs could play a functional role in tumor progression.
authors.affiliation: Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Satish Kumar
authors.initials: SK
authors.lastname: Ramraj
authors.affiliation: Stephenson Cancer Center, Oklahoma City, OK, USA.
authors.forename: Sheeja
authors.initials: S
authors.lastname: Aravindan
authors.affiliation: Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Dinesh Babu
authors.initials: DB
authors.lastname: Somasundaram
authors.affiliation: Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Stephenson Cancer Center, Oklahoma City, OK, USA.
authors.forename: Terence S
authors.initials: TS
authors.lastname: Herman
authors.affiliation: Department of Pathology, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA.
authors.forename: Mohan
authors.initials: M
authors.lastname: Natarajan
authors.affiliation: Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Aravindan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D064593:Heterografts; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D009362:Neoplasm Metastasis; D009447:Neuroblastoma / Q000097:blood* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012307:Risk Factors
chemical_list: D035683:MicroRNAs
keywords: high-risk metastatic neuroblastoma; miRnome profiling; prognostic biomarker; serum-circulating miRNA