TMPO-AS1-hsa-let-7b-5p-EZH2-RNA network predicts poor survival in basal-like breast cancer patients

The study explores the role of non-coding ribonucleic acids (ncRNAs) and higher enhancer of zeste homolog 2 (EZH2) gene in breast cancer progression, examining how microRNA (miRNA) and long noncoding RNA (lncRNA) control EZH2, potentially influencing oncogene growth and treatment failure.

The databases used in the study included Cyclebase 3.0 and CellTracer to determine EZH2's role in cell cycle, Oncomine, OncoMX and The University of Alabama At Birmingham Cancer Data Analysis Portal (UALCAN) for Pan-cancer analysis, The Cancer Genomic Atlas Portal (TCGA Portal), Gene Expression Profiling Interactive Analysis (GEPIA2), OncoDB, CR2Cancer, Encyclopaedia of RNA Interactomes (ENCORI), and The Cancer Genome Altas Analyzer (TCGAnalyzeR v1.0) for differential expression analysis, CR2Cancer, OncoDB, MethMarkerDB, and Wanderer databases for epigenetic alteration analysis, Kaplan-Meier Plotter for survival analysis, Breast Cancer Gene Expression Miner (bc-GenExMiner v5.0) for hormone receptor analysis, Tumor-Immune System Interaction Database (TISIDB), Cancer Single Cell State Atlas (CancerSEA), TNMplot, DriverDBv4, and ENCORI for biological processes, cell cycle checkpoints and metastasis analysis, Enrichr, Tumor Immune Estimation Resource (TIMER 2.0), Gepia2 for transcription factor analysis, miRNet, Transcriptome Alterations in Cancer Omnibus (TACCO), and CancerMIRome for miRNA analysis, Enrichr, UALCAN, and ENCORI for lncRNA analysis.

The EZH2 gene is overexpressed in breast cancer (BRCA) tumors, metastatic tissues, and circulating tumor cells, potentially leading to cancer progression. Patients with high EZH2 expression have shorter overall survival (OS), distant metastasis-free survival (DMFS), and relapse-free survival (RFS) compared to those with low expression. Estrogen receptot (ER)-negative BRCA tumors and PR-negative tumors have high EZH2 gene and eukaryotic transcription factor (E2F2) levels. The EZH2/E2F2 axis may assist ER/PR-negative BRCA by sponging homosapiens microRNA family (hsa-let-7b-5p) through lncRNA-thymopoietin antisense transcript 1 (TMPO-AS1). Overexpression of the EZH2 protein is associated with BRCA metastasis.

EZH2 overexpression in basal-like BRCA is mediated by a competing endogenous RNA (ceRNA) network and regulating their expression levels may facilitate better survival outcomes.