Endogenous retroviruses mediate transcriptional rewiring in response to oncogenic signaling in colorectal cancer.

ABSTRACT: Cancer cells exhibit rewired transcriptional regulatory networks that promote tumor growth and survival. However, the mechanisms underlying the formation of these pathological networks remain poorly understood. Through a pan-cancer epigenomic analysis, we found that primate-specific endogenous retroviruses (ERVs) are a rich source of enhancers displaying cancer-specific activity. In colorectal cancer and other epithelial tumors, oncogenic MAPK/AP1 signaling drives the activation of enhancers derived from the primate-specific ERV family LTR10. Functional studies in colorectal cancer cells revealed that LTR10 elements regulate tumor-specific expression of multiple genes associated with tumorigenesis, such as ATG12 and XRCC4. Within the human population, individual LTR10 element

SUBMITTER: Ivancevic A 

PROVIDER: S-EPMC466953 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature