Genome-wide enhancer RNA profiling adds molecular links between genetic variation and human cancers

Area of Science:

• Genomics and Cancer Biology
• Molecular Mechanisms of Gene Regulation

Background:

• Dysregulation of enhancer transcription is implicated in various cancers.
• Enhancer RNAs (eRNAs) are key regulators of gene transcription.
• Understanding the genetic basis of eRNA expression can reveal cancer mechanisms.

Purpose of the Study:

• To characterize eRNA quantitative trait loci (eRNAQTLs) across diverse cancer types.
• To establish eRNAQTL profiles for Chinese colorectal cancer (CRC) patients.
• To investigate the functional mechanisms of eRNAQTLs in CRC risk.

Main Methods:

• Analysis of eRNAQTLs in The Cancer Genome Atlas (TCGA) and multi-omics data.
• Integration of epigenomic, transcription, and genotyping data from 154 CRC samples.
• Large-scale case-control studies (34,585 cases, 69,544 controls) and experimental validation.

Main Results:

• Identified 300,112 eRNAQTLs across 30 cancer types, influencing eRNA transcription and chromatin status.
• eRNAQTLs are enriched in cancer risk loci, contributing to cancer heritability.
• A specific eRNAQTL variant (rs3094296-T) decreases CRC risk in Chinese and European populations by modulating eRNA ENSR00000155786 and SENP7 expression.

Conclusions:

• eRNAQTLs play a significant role in transcriptional regulation and disease heritability.
• These findings highlight the potential of eRNA-based therapeutic strategies for cancer treatment.
• A comprehensive database (CancereRNAQTL) is established for further research.