Enhancer RNAs in Acute Myeloid Leukemia: Potential Diagnostic Biomarkers Revealed by RNA-Seq

Acute myeloid leukemia (AML) is a group of malignant diseases that arise from bone marrow hematopoietic stem cells. Despite a comprehension of its pathogenesis, mortality rates remain high. Adverse outcomes can be related to delayed diagnosis and failure to achieve complete remission. This issue highlights the urgent need to find diagnostic and prognostic markers from RNA sequencing (RNA-Seq) data. Over a decade, the rapid adoption and development of high-throughput sequencing technologies offered a novel chance to investigate non-coding RNAs. Enhancer RNAs (eRNAs) are a category of non-coding RNAs transcribed from enhancer sites. While modifications in the expression and functional roles of eRNAs in several cancer types have been documented, the comprehension of eRNAs and their prospective functions in AML remains significantly constrained. The present investigation employed in-silico approaches to evaluate transcriptome data and discover eRNAs as potential biomarkers for better prognosis and diagnosis of AML. Methods: The AML RNA-seq samples used in the study were obtained from the Sequence Read Archive (SRA). FASTQ files were subsequently aligned to the ENSEMBL hg۳۸ genome assembly. To acquire the raw count of eRNAs and protein-coding genes, the enhancer site annotation file and GTF annotation were downloaded from the FANTOM۵ project and Ensemble database, respectively. Differential expression analysis was conducted to identify genes and eRNAs that exhibit concordant expression changes (i.e., either upregulated or downregulated) between AML and normal samples. Furthermore, to examine the eRNA gene relationships, a co-expression analysis was performed, and a co-expression network was constructed between eRNAs and their target genes. Ultimately, to discover and investigate potential associated pathways, functional enrichment analyses were applied for differentially expressed genes (DEGs) and target genes of differentially expressed eRNAs (DEeRNAs). Results: Our investigation showed increased expression levels of chr۲۲.۲۹۱۹۹۷۶۷-۲۹۱۹۹۹۵۳ in AML samples relative to normal samples (|log۲FC >۱| and FDR<۰> ۰.۶, FDR < ۰.۰۱). Furthermore, the use of functional enrichment analysis to identify pathways associated with this eRNA revealed that chr۲۲.۲۹۱۹۹۷۶۷-۲۹۱۹۹۹۵۳ functions in the MYC targets v۱ pathway, and its target genes mediate the progression of AML. Conclusion: This study revealed for the first time that chr۲۲.۲۹۱۹۹۷۶۷-۲۹۱۹۹۹۵۳ expression is elevated in AML. The identification of chr۲۲.۲۹۱۹۹۷۶۷-۲۹۱۹۹۹۵۳-associated genes and pathways provides a new understanding of the molecular mechanisms underlying the initiation and progression of AML through eRNAs. These findings highlight chr۲۲.۲۹۱۹۹۷۶۷-۲۹۱۹۹۹۵۳ as a promising candidate for further investigation and emphasize the potential of eRNAs as biomarkers in AML, which could help with early diagnosis and therapy approaches.

کلیدواژه ها:

Non-coding RNA ، AML ، Enhancer RNA ، Differential expression analysis ، RNA-seq