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Disruption of metazoan gene regulatory networks in cancer alters the balance of co-expression between genes of unicellular and multicellular origins.
Trigos, Anna S; Bongiovanni, Felicia; Zhang, Yangyi; Zethoven, Maia; Tothill, Richard; Pearson, Richard; Papenfuss, Anthony T; Goode, David L.
Afiliación
  • Trigos AS; Peter MacCallum Cancer Centre, 305 Grattan St., Melbourne, VIC, 3000, Australia. anna.trigos@petermac.org.
  • Bongiovanni F; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, 3010, Australia. anna.trigos@petermac.org.
  • Zhang Y; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3168, Australia. anna.trigos@petermac.org.
  • Zethoven M; Peter MacCallum Cancer Centre, 305 Grattan St., Melbourne, VIC, 3000, Australia.
  • Tothill R; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, 3010, Australia.
  • Pearson R; Peter MacCallum Cancer Centre, 305 Grattan St., Melbourne, VIC, 3000, Australia.
  • Papenfuss AT; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, 3010, Australia.
  • Goode DL; Peter MacCallum Cancer Centre, 305 Grattan St., Melbourne, VIC, 3000, Australia.
Genome Biol ; 25(1): 110, 2024 04 29.
Article en En | MEDLINE | ID: mdl-38685127
ABSTRACT

BACKGROUND:

Metazoans inherited genes from unicellular ancestors that perform essential biological processes such as cell division, metabolism, and protein translation. Multicellularity requires careful control and coordination of these unicellular genes to maintain tissue integrity and homeostasis. Gene regulatory networks (GRNs) that arose during metazoan evolution are frequently altered in cancer, resulting in over-expression of unicellular genes. We propose that an imbalance in co-expression of unicellular (UC) and multicellular (MC) genes is a driving force in cancer.

RESULTS:

We combine gene co-expression analysis to infer changes to GRNs in cancer with protein sequence conservation data to distinguish genes with UC and MC origins. Co-expression networks created using RNA sequencing data from 31 tumor types and normal tissue samples are divided into modules enriched for UC genes, MC genes, or mixed UC-MC modules. The greatest differences between tumor and normal tissue co-expression networks occur within mixed UC-MC modules. MC and UC genes not commonly co-expressed in normal tissues form distinct co-expression modules seen only in tumors. The degree of rewiring of genes within mixed UC-MC modules increases with tumor grade and stage. Mixed UC-MC modules are enriched for somatic mutations in cancer genes, particularly amplifications, suggesting an important driver of the rewiring observed in tumors is copy number changes.

CONCLUSIONS:

Our study shows the greatest changes to gene co-expression patterns during tumor progression occur between genes of MC and UC origins, implicating the breakdown and rewiring of metazoan gene regulatory networks in cancer development and progression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Redes Reguladoras de Genes / Neoplasias Límite: Animals / Humans Idioma: En Revista: Genome Biol Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Redes Reguladoras de Genes / Neoplasias Límite: Animals / Humans Idioma: En Revista: Genome Biol Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido