Transposable Elements Expression in the Context of Cancer and Stem Cell Maintenance

Transposable elements (TE) are mobile DNA elements that can replicate and re-insert themselves into different locations within the host genome. This retrotransposition has resulted in TEs accounting for more than 50% of the human genome. Much like other non-coding RNAs, TE insertions with multiple copies were once considered non-functional. But recently it has been shown to have much more regulatory role in different cellular pathways. The first part of this thesis delves in describing the different types of TE and other non-coding RNAs like non-coding RNA and their significance in inflammation and cancer. Noncoding and repeat-derived cell-free RNA transcriptome (TE) is a rich source of novel, abundant, and disease-specific RNA biomarkers. We show that repeat-derived cell-free RNAs, including simple repeat RNAs and TE RNAs transcribed from LINE, SINE, and LTR elements, are cancer-specific RNAs that are normally present at low or undetectable levels in healthy individuals. The second part explains about the role of RAS in regulating TE in the context of cancer. Here I describe about RAS effector transcripts give rise to a diverse array of non-coding RNAs that contribute significantly to cancer initiation and progression. Our study also reveals the transcriptomic and epigenomic impact of oncogenic KRAS signaling on TE RNAs and ISGs. Our study suggests that KZNF repression by mutant KRAS signaling leads to de-repression of TE RNAs, triggering an intrinsic ISG response. This model is supported by broad and significant downregulation of these same KNZFs in mutant KRAS-driven lung adenocarcinomas in vivo. We also identified mutant KRAS(G12C)-specific exRNA signatures secreted from LUAD cells by comprehensively analyzing the coding and noncoding RNAs secreted in extracellular vesicles (EV). The final section addresses the regulation of transposable elements (TEs) by KRAS during the pluripotency and differentiation of human induced pluripotent stem cells (hiPSCs). My resear