Minor Intron Genes as Potential Targets for Affecting Survival of Triple-Negative Breast Cancer Cells

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 regulating their splicing. Previous work on this project evaluated the splicing of 30 minor intron genes in breast cancer cells by manipulating levels of U6atac expression within the cells. This led to the categorization of minor intron genes into two classes. This research explores why these classes exist by studying protein functionality and micro-RNA binding sites within these genes. Additionally, it explores the lowest dose at which U6atac snRNA can be inhibited to selectively kill breast cancers cell by affecting the splicing of particularly sensitive minor intron genes. This research focuses on triple-negative breast cancer using MDA-MB-231 cells as a model. Overall, this research aims 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.