Bioinformatics insights into TMPO-AS1–let-7b-5p–ESPL1/E2F8 regulatory axis in breast cancer

We found that <i>ESPL1</i> gene was significantly overexpressed in tumors, metastatic tissues, and circulating tumor cells, with tumor samples showing an overall 4-fold increase in expression compared to adjacent normal tissue of BC patients. Furthermore, BC patients with high <i>ESPL1</i> expression exhibited shorter overall survival (OS), disease-free survival (DFS), and relapse-free survival (RFS) compared to patients with low expression. Tumors from ER-negative and PR-negative BC patients exhibited elevated expression levels of both <i>ESPL1</i> and the transcription factor <i>E2F8</i>. Moreover, increased levels of <i>ESPL1</i> and <i>E2F8</i> were positively correlated with lncRNA <i>TMPO-AS1</i>, while negatively correlated with <i>hsa-let-7b-5p</i>. Notably, the 3' untranslated region (3'UTR) of <i>ESPL1</i> showed strong binding sites for <i>hsa-let-7b-5p</i>. We also identified Hesperidin as a high affinity <i>ESPL1</i> binders, suggesting novel therapeutic candidates targeting this oncogenic network.