Type

Journal Article

Authors

Raymond L Stallings
Louis Chesler
Hannah Webber
Albert Hallsworth
Lynsey Vaughan
Kenneth Bryan
Marta Terrile

Subjects

Biochemistry

Topics
disease models animal gene expression profiling mice proto oncogene proteins cell line tumor mice transgenic tumor suppressor protein p53 neuroblastoma humans micrornas mycn protein mouse adrenal glands cluster analysis genetics signal transduction animals metabolism gene expression regulation neoplastic

miRNA expression profiling of the murine TH-MYCN neuroblastoma model reveals similarities with human tumors and identifies novel candidate miRNAs. (2011)

Abstract MicroRNAs are small molecules which regulate gene expression post-transcriptionally and aberrant expression of several miRNAs is associated with neuroblastoma, a childhood cancer arising from precursor cells of the sympathetic nervous system. Amplification of the MYCN transcription factor characterizes the most clinically aggressive subtype of this disease, and although alteration of p53 signaling is not commonly found in primary tumors, deregulation of proteins involved in this pathway frequently arise in recurrent disease after pharmacological treatment. TH-MYCN is a well-characterized transgenic model of MYCN-driven neuroblastoma which recapitulates many clinicopathologic features of the human disease. Here, we evaluate the dysregulation of miRNAs in tumors from TH-MYCN mice that are either wild-type (TH-MYCN) or deficient (TH-MYCN/p53ER(TAM)) for the p53 tumor suppressor gene. We analyzed the expression of 591 miRNAs in control (adrenal) and neuroblastoma tumor tissues derived from either TH-MYCN or TH-MYCN/p53ER(TAM) mice, respectively wild-type or deficient in p53. Comparing miRNA expression in tumor and control samples, we identified 159 differentially expressed miRNAs. Using data previously obtained from human neuroblastoma samples, we performed a comparison of miRNA expression between murine and human tumors to assess the concordance between murine and human expression data. Notably, the miR-17-5p-92 oncogenic polycistronic cluster, which is over-expressed in human MYCN amplified tumors, was over-expressed in mouse tumors. Moreover, analyzing miRNAs expression in a mouse model (TH-MYCN/p53ER(TAM)) possessing a transgenic p53 allele that drives the expression of an inactive protein, we identified miR-125b-3p and miR-676 as directly or indirectly regulated by the level of functional p53. Our study represents the first miRNA profiling of an important mouse model of neuroblastoma. Similarities and differences in miRNAs expression between human and murine neuroblastoma were identified, providing important insight into the efficacy of this mouse model for assessing miRNA involvement in neuroblastoma and their potential effectiveness as therapeutic targets.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Raymond L Stallings, Louis Chesler, Hannah Webber, Albert Hallsworth, Lynsey Vaughan, Kenneth Bryan, Marta Terrile

Experts in our system

1
Raymond L Stallings
Royal College of Surgeons in Ireland
Total Publications: 59
 
2
Kenneth Bryan
Royal College of Surgeons in Ireland
Total Publications: 36