| Popis: |
Genes with minor introns are involved in DNA damage repair, cell cycle, replication, transcription, and cell signalling, strongly associating them with certain cancers upon misregulation. U6atac snRNA (small nuclear RNA) coded by the U6atac gene, the catalytic component of the minor spliceosome, regulates the expression of minor introns genes by mediating their splicing. Previous work done in Younis lab evaluated the splicing of 30 minor intron genes in breast cancer cells by manipulating U6atac levels. This led to the categorization of minor intron genes into two classes. This research explored why these classes exist by studying protein functionality and micro-RNA binding sites within these genes. No concrete reason for Class-specific splicing patterns was identified. However, promising approaches in terms of sequence similarity and potential motifs within minor introns of Class I, II genes were initiated. Additionally, this research explored a low critical dose at which U6atac snRNA can be inhibited to selectively kill breast cancers cell by affecting the splicing of particularly sensitive minor intron genes. 0.5uM U6atac AMO dose was found to be this dose. This research focused on triple-negative breast cancer using MDA-MB-231 cells as a model. Overall, it aimed to broaden understanding of specific minor intron genes, their behaviour in triple-negative breast cancer, and how they can be manipulated for a therapeutic advantage. |
