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Gene expression signatures for HOXA4, HOXA9, and HOXD10 reveal alterations in transcriptional regulatory networks in colon cancer
Journal article   Peer reviewed

Gene expression signatures for HOXA4, HOXA9, and HOXD10 reveal alterations in transcriptional regulatory networks in colon cancer

Seema Bhatlekar, Adam Ertel, Gregory E Gonye, Jeremy Z Fields and Bruce M Boman
Journal of cellular physiology, v 234(8), pp 13042-13056
Aug 2019
DOI: https://doi.org/10.1002/jcp.27975
PMID: 30552679
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Colonic Neoplasms - genetics Colonic Neoplasms - pathology Gene Expression Regulation, Neoplastic - physiology Gene Regulatory Networks Homeodomain Proteins - biosynthesis Homeodomain Proteins - genetics Humans Neoplastic Stem Cells - metabolism Neoplastic Stem Cells - pathology Transcription Factors - biosynthesis Transcription Factors - genetics Transcription Factors - metabolism Transcriptome
We previously reported that HOXA4, HOXA9, and HOXD10 are selectively expressed in colonic stem cells (SCs) and their overexpression contributes to colorectal cancer (CRC). Our goals here were to determine how these HOX genes are transcriptionally regulated and whether transcriptional dysregulation of HOX genes occurs in CRC. Accordingly, we used correlation analysis to identify genes that are expression-correlated or anticorrelated with HOXA4, HOXA9, and HOXD10. We then used Gene Ontology (GO) analysis to functionally classify these genes. The GO results for both HOXA4 and HOXD10 correlated gene sets for normal colon and CRC show functions mostly classified as developmental, transcriptional regulation, and DNA binding. This raised the question: Are these gene sets regulated by the same transcription factors (TFs)? Consequently, we used promoter analysis and interaction network toolset (PAINT) to identify commonly shared transcription response elements. The results indicated that completely different sets of TFs coregulate HOXA4 and HOXD10 (but not HOXA9) and their expression-correlated genes. And predicted TFs are altered in CRC compared with normal colon. Taken together, analysis of gene signatures correlated with expression of HOXA4 and HOXD10 indicates how these HOX genes are: (a) transcriptionally regulated in the normal colon; (b) dysregulated in CRC. This discovery provides a mechanism for targeting CRC SCs.

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12 citations in Scopus

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Collaboration types
Industry collaboration
Domestic collaboration
Web of Science research areas
Cell Biology
Physiology
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