Alhumam Alkhusheh

University of Nottingham

Investigating the effect of the PRH transcription factor on gene expression in bile duct cancer cells

Biography

Abstract

Background: The proline rich homeodomain (PRH) protein is one of the few discovered proteins that cannot be classified exclusively as an oncogene or a tumour suppressor. It is proposed to have dual tumour suppressive and oncogenic action, dependent on location and condition. Both overexpression and downregulation of PRH have led to increases in malignancy. Bile duct cancer, also known as cholangiocarcinoma (CCA), is an example of overexpression of PRH acting in an oncogenic manner.

Objectives: The primary aim of the study was to use data analysis techniques to identify directly regulated genes by PRH in CCA and observe how PRH interacts with these genes.

Methods: A variety of data analytical methods were implemented on RNA sequencing and chromatin immunoprecipitation (ChIP) sequencing datasets, obtained from experiments on a human CCA cell line (CCLP1). The overlap between both datasets determined which genes are directly regulated by PRH.

Results: A set of 74 genes, directly regulated by PRH, was curated. Of these, 6 repeatedly emerged in Gene Set Enrichment Analysis (GSEA) results, revealing enrichment in multiple different signature gene sets. These 6 genes were investigated and discussed: Integrin Beta 4 subunit (ITGB4), Krupper Like Factor 5 (KLF5), SRY-Box Transcription Factor 9 (SOX9), GATA binding protein 3 (GATA3), Regulator of G Protein Signalling 1 (RGS1) and Regulator of G Protein Signalling 2 (RGS2).

Conclusions: Further evidence was shown to prove the simultaneous action of PRH as an oncogene and tumour suppressor, whilst proposing several new links between PRH and these genes, unbeknownst to current literature. The identification of the genes discussed warrants further investigation and exploration into their potential as novel biomarkers or therapeutic targets in CCA.