Year: 2018
Type: dissertation
Abstract: An epigenetic drug screen was carried out in CRC organoids which identified PRMT5 as a potential epigenetic target regulating CC-ICs. Upon analyzing a cohort of CRC patients from TCGA, PRMT5 mRNA was observed to be significantly upregulated in tumour samples compared to normal. This evidence led us to pursue further work using CC-IC enriched cell lines to understand the functional role of PRMT5. Pharmacological inhibition of PRMT5 decreased cell viability in three CC-IC enriched cell lines. In contrast, genetic knockdown of PRMT5 using shRNA increased or had no effect on cell viability. Pretreatment of CC-IC enriched spheres using PRMT5 inhibitors led to an increase in Wnt-reporter activity. No effect on CC-IC stem cell frequency was observed upon pharmacologically or genetically inhibiting PRMT5. Next, we explored the oncogenic role of PRMT5 in normal organoids. Upon overexpression of PRMT5 in normal and engineered normal organoids, no difference in proliferation was observed.
Source: TSpace (University of Toronto)
Author: Judy Truong
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2941549487