Long non-coding RNA TMPO-AS1 promotes aggressive triple-negative breast cancer by sponging hsa-let-7b-5p-mediated AURKB upregulation
Aurora kinase B (AURKB), a regulator of mitosis, is associated with aggressive breast cancer (BRCA) and poor patient outcomes, although its exact role remains unclear. This study performed an in silico analysis to investigate AURKB expression, regulation, and prognostic relevance in BRCA. Differential expression of AURKB was evaluated using the University of Alabama Cancer Database (UALCAN), the Encyclopedia of RNA Interactomes (ENCORI), OncoDB, The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and TCGAnalyzeR v1.0. Survival analysis was conducted using the Kaplan–Meier plotter database, and subtype-specific associations were examined using the TCGA portal, the Tumor-Immune System Interactions and Drug Bank database, Breast Cancer Gene- Expression Miner v5.0 (bc-GenExMinerv5.0), UALCAN, and ENCORI. AURKB’s role in biological processes and metastasis was studied using the Cancer Single-cell State Atlas, TNMplot, and ExploRRNet. Transcription factors associated with AURKB were analyzed using Enrichr, ENCORI, Tumor Immune Estimation Resource, GEPIA2, OncoDB, UALCAN, and bc-GenExMinerv5.0. MicroRNAs were examined using miRNet, Transcriptome Alterations in Cancer Omnibus, CancerMIRNome, and ENCORI, while long non-coding RNAs were studied using ENCORI, OncoDB, UALCAN, and TCGAnalyzeR v1.0. Elevated AURKB levels were linked to decreased distant metastasis-free survival (Hazard ratio [HR] = 1.71), relapse-free survival (HR = 1.43), and overall survival (HR = 1.45). AURKB transcripts also showed elevated expression in BRCA with a log2 fold change of 3.03. A novel competing endogenous RNA (ceRNA) network was identified, where AURKB correlated positively with E2F1 (r = 0.806) and TMPO-AS1 (r = 0.610) but negatively with hsa-let-7b-5p (r = −0.452). TMPO-AS1 also showed a negative correlation with hsa-let-7b-5p (r = −0.204). High E2F1 expression was associated with worse OS (HR = 1.53), whereas higher hsa-let- 7b-5p levels were linked to better prognosis (HR = 0.68). Binding affinity predictions supported interactions between hsa-let-7b-5p and AURKB, E2F1, ESR1, PGR, and TMPO-AS1 (−16.40, −90, −50, −90, and −40 kcal/mol, respectively). Overall, AURKB dysregulation through this ceRNA network may promote BRCA progression, offering potential for new prognostic biomarkers and personalized therapies.
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