Disruption of metazoan gene regulatory networks in cancer alters the balance of co-expression between genes of unicellular and multicellular origins
02:22 Share

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.20.537744v1?rss=1

Authors: Trigos, A. S., Bongiovanni, F., Zethoven, M., Tothill, R., Pearson, R. B., Papenfuss, A. T., Goode, D. L.

Abstract: Metazoans inherited genes from unicellular ancestors that perform essential biological processes such as cell division, metabolism and protein translation. Functioning multicellularity requires careful control and coordination of these unicellular genes to maintain tissue integrity and homeostasis. Gene regulatory networks (GRNs) formed during metazoan evolution to regulate conserved biological processes are frequently altered in cancer, resulting in over-expression of unicellular genes. We propose an imbalance in co-expression of unicellular (UC) and multicellular (MC) genes is a driving force in cancer. To investigate, we combined 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 tumour types and normal tissue samples were divided into modules enriched for UC genes, MC genes or a mix of both (Mixed UC-MC modules). The greatest differences between tumour and normal tissue co-expression networks occurred within Mixed UC-MC modules. In particular, MC and UC genes not commonly co-expressed in normal tissues formed distinct co-expression modules seen only in tumours. The degree of rewiring of genes within Mixed UC-MC modules increased with both tumour grade and stage. Mixed UC-MC modules were enriched for somatic mutations in cancer genes, particularly copy-number amplifications, suggesting an important driver of the rewiring observed in tumours are copy-number changes. Overall, our study shows the greatest changes to gene co-expression patterns during tumour progression occur between genes of MC and UC origins, implicating the breakdown and rewiring of metazoan gene regulatory networks in cancer development and progression.

Copy rights belong to original authors. Visit the link for more info

Podcast created by Paper Player, LLC