Molecular Effects of Glucose on MIR503HG-Regulated Genes in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, characterized by a lack of key hormone receptors in tumor cells. As there are limited treatment options for these patients, it is crucial to understand the underlying mechanisms by which TNBC constantly evolves and evades treatments. In this regard, the pervasive nature of transcription provides a potential reservoir of transcripts, including both coding and noncoding, that TNBC leverages to sustain a proliferative advantage and support tumor growth. TNBC is affected by energy sources such as glucose, which can have a profound impact on gene expression regulation mediated by various molecules, including noncoding RNAs, at the cellular level. In this study, we demonstrate that glucose modulates the gene expression profile mediated by the microRNA-503 host gene (MIR503HG), which has been previously implicated in TNBC. To comprehensively characterize the impact of glucose on MIR503HG-regulated genes and cellular pathways, we sequenced total RNA, performed gene set enrichment analyses, and determined the relation between gene expression and patient outcomes. Analysis of gene subsets specific to various glucose environments identified clinical outcomes for breast cancer patients across different molecular subtypes. Our findings indicate that MIR503HG has potential as a diagnostic marker and may be useful in the clinical management of TNBC.