The Hidden Oncogenic Architects: The Role of Transposable Elements in Cis-Regulation and Genomic Architecture in Cancer

Transposable elements (TEs) comprise nearly half of the human genome and contain a reservoir of cis-regulatory and 3D genome altering sequences. The potential for genomic and transcriptional disruption has led to the epigenetic repression of TEs through multiple cooperating mechanisms. The disruption of these epigenetic mechanisms in cancer and the consequent derepression of TEs leads to widespread functional impacts that are both pro- and anti-tumorigenic. This review explores the methods employed by cells to repress TEs and the effect of their dysregulation on cis-regulation, immunogenicity, and 3D genome architecture. Through this, we show the functional importance of this derepression in cancer across different structural levels, highlighting contemporary work exploring and explaining the complexity of TE regulation in cancer.