Enhancer RNAs (eRNAs) are noncoding RNA. While dysregulation of eRNAs in the development of several cancers has been reported, the specific information regarding the landscape of eRNAs in acute myeloid leukemia (AML) is minimal.
RNA-sequencing data were retrieved from the SRA database and aligned to the human reference genome (hg38) from Ensembl. Enhancer site annotations from the FANTOM5 project and gene annotations from Ensembl were used to obtain raw expression counts for eRNAs and protein-coding genes. Differential expression and co-expression analyses were performed to identify eRNAs associated with AML and their potential co-expressed genes. Functional enrichment analysis was used to determine biological pathways associated with the co-expressed genes of eRNAs. Two eRNAs associated with AML-related pathways were selected for experimental validation using real-time PCR.
Two eRNAs, designated eRNA-7A (chr7:157299821–157300521, (hg38)) and eRNA-22A (chr22:29199767–29199953, (hg38)), were significantly upregulated in AML samples compared with normal controls. Real-time PCR confirmed their elevated expression levels in AML patients. Co-expression and functional enrichment analyses identified genes and pathways associated with these eRNAs, showing that genes positively correlated with eRNA-7A and eRNA-22A were significantly enriched in the Myc targets v1 and v2 pathways. Notably, several enriched genes in these pathways have been previously linked to AML pathogenesis.
The eRNAs identified in this study, along with their associated genes and pathways, provide a preliminary understanding of the molecular mechanisms underlying AML development and progression. Moreover, they suggest the existence of promising candidates for future biomarker development in AML.