Abstract
Cancer is characterized by dysregulation at multiple levels, such as gene transcription. Enhancers are well-studied transcription regulators that can enhance target transcripts through DNA loop formation mediated by chromosome folding. The gain or loss of the interaction between an enhancer and its target gene has a critical effect on gene expression. In this study, we analyzed GRO-seq data to identify active enhancers from seven common cancer cell lines and studied the function of these enhancers across multiple cancer types. By constructing an “enhancer effect score” (EES), we found a significant correlation between EES and tumor-infiltrating lymphocytes (TILs) in prostate cancer. Further analysis revealed that androgen receptor (AR) plays an important role in regulating the immune checkpoint gene PVR via its enhancer. These results suggest that AR contributes to prostate cancer aggressiveness by promoting cancer cell immune evasion.
Highlights
IntroductionCancer cells possess some common features, such as genome instability and unlimited replicative potential, which are known as cancer hallmarks (Hanahan and Weinberg, 2000, 2011)
Cancer is one of the leading causes of death
The importance of these enhancers was further investigated in cancer databases, and the results revealed that these enhancers are important for regulating cancer signaling pathways and cancer hallmarks
Summary
Cancer cells possess some common features, such as genome instability and unlimited replicative potential, which are known as cancer hallmarks (Hanahan and Weinberg, 2000, 2011). The emergence of these cancer hallmarks is driven by mutations accumulated during the process, in which normal cells transform tissue to states from hyperplasia to dysplasia until neoplasia is established. Large-scale genomewide studies (GWASs) of cancer patients have indicated that dysregulation of gene expression significantly contributes to cancer development (Sarkar et al, 2013). Enhancers play important roles in driving oncogene transcription and may determine some cell-specific traits
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