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Open Access

Reprogramming the human cancer cell nucleus

  • John Frenster1 and
  • Jeannette Hovsepian2
Genome Biology201011(Suppl 1):P14

Published: 11 October 2010


Gene ClusterNeuroblastomaNeoplastic CellNoncoding RNAsHuman Neuroblastoma Cell


The human cancer cell nucleus contains 46 or more chromosomes, each bearing portions of the human genome. During the initiation and progression of the neoplastic state, chromosome portions can be duplicated, deleted, translocated or inverted, and these lesions often aggravate the rate of progression and metastasis of the cells. During gene transcription, two or more chromosomes can form gene clusters at specific gene sites, and such clusters regulate the rate of gene transcription and replication. Gene clusters are often sensitive to the immediate effects of ligand microRNAs (miRNAs) and other transcribed ultra-conserved noncoding RNAs (T-UCRs). Recent studies have reported 481 species of T-UCRs within human neuroblastoma cells, mostly from intragenic exon and/or intron sequences within the Ref-seq genome, but 37% were found transcribed from noncoding intergenic sites in the neoplastic cell genome [1]. In 237 of the 481 T-UCRs, intra-nuclear functions were completely independent of those within coding and other nuclear RNAs, and were increased in neuroblastomas of an aggressive type. Most of the T-UCRs could be found in linked regions of 4 major gene clusters, associated with the 4 nuclear processes of neoplastic proliferation, apoptosis, differentiation, and patient survival. Similar T-UCR RNA patterns in normal human fibroblast BJ cells were also observed [1]. Earlier observations had demonstrated a specific deficiency of let-7 RNA microRNA species within human lung and breast neoplasms, that was reversed by the addition of let-7 RNA species to the neoplastic cells in culture [2, 3].


It appears that microRNAs and perhaps T-UCRs may well be able to reverse the neoplastic state within animals with metatstatic neoplasms, and these RNAs can be delivered as liposomal exosomes [4].

Authors’ Affiliations

Department of Medicine, Stanford University, Stanford, USA
Department of Radiology, Stanford University, Stanford, USA


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© Frenster and Hovsepian; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd.