Identification and validation of novel targets of regulated IRE1-dependent decay in triple-negative breast cancer
Denny, Amy
Denny, Amy
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Publication Date
2025-10-08
Type
master thesis
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Abstract
IRE1 is a primary effector of the unfolded protein response that aims to restore proteostasis to the endoplasmic reticulum. IRE1 possesses a kinase and RNase domain. The RNase activity is responsible for two of the main activities of IRE1 signalling, i.e., removal of a 26-nucleotide sequence to form XBP1s transcription factor and regulated IRE1 dependent decay (RIDD) of RNA. RIDD reduces the expression of genes termed ‘RIDD targets’ by cleavage of CG sequence at a CNGCNG sequence within a stem-loop structure.
IRE1 is constitutively active in triple negative breast cancer. RIDD has a known role in influencing lipid metabolism in triple negative breast cancer via its activity on DGAT2. Identifying additional RIDD target genes could enable us to better understand the role of IRE1 in this cancer.
Bioinformatic analysis was carried out in our lab to identify genes upregulated by IRE1 inhibition in MDA-MB-231 triple negative breast cancer cells. This project aims to add to our understanding of RIDD in the regulation of those genes by validating these potential targets in MDA-MB-231 cells.
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University of Galway
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CC BY-NC-ND