Background: This study sought to identify the downstream target genes of enolase 1 (ENO1), clarify the role of ENO1 in gastric cancer (GC), and provide novel insights into the regulatory mechanisms of ENO1 in the occurrence and development of GC.
Methods: We performed RNA-immunoprecipitation sequencing in MKN-45 cells to study the types and abundance of pre-messenger RNA (mRNA)/mRNA bound by ENO1, the binding sites and motifs, the relationship between ENO1 binding and its regulation of transcription level, and alternative splicing level by combining with RNA-sequencing (RNA-seq) data to further clarify the role of ENO1 in GC.
Results: We found that ENO1 stabilized the expression of SRY-box transcription factor 9 (SOX9), vascular endothelial growth factor A (VEGFA), G protein-coupled receptor class C group 5 member A (GPRC5A), and myeloid cell leukemia-1 (MCL1) by binding to their mRNA, which increased the growth of GC. In addition, ENO1 interacted with some other long non-coding RNAs (lncRNAs) or small-molecule kinases, such as NEAT1, LINC00511, CD44, and pyruvate kinase M2 (PKM2), to regulate their expression to affect cell proliferation, migration, and apoptosis.
Conclusions: ENO1 may play a role in GC by binding to and regulating GC-related genes. Our findings extend understandings of its mechanism as a clinical therapeutic target.
Keywords: RNA-binding protein; gastric cancer (GC); glycolysis; glycolytic pathway enolase 1; pyruvate kinase M2 (PKM2).
2023 Journal of Gastrointestinal Oncology. All rights reserved.