Differential expression of the lncRNA MIR17HG and miR-18a/miR-20a as candidate ncRNA signatures in stage II/III breast cancer and bioinformatic analysis of ncRNA–mRNA regulatory axes

Abstract

Objective(s): Breast cancer has remained a significant cause of mortality associated with cancer, necessitating a deeper molecular understanding to improve diagnostics and targeted therapies. Noncoding RNAs (ncRNAs) and their regulatory ncRNA–mRNA axes have recently emerged as important modulators of cancer progression and potential tools for earlier detection and more precise stratification of breast cancer. Among them, MIR17HG variants and the precise regulatory axes of miR-18a/miR-20a, and their mechanisms in stage II/III BC, remain elusive. Materials and Methods: This study addresses this critical gap by integrating data from TCGA miRNAseq and RNAseq datasets with experimental qRT-PCR validation on patient tissues. We investigate MIR17HG transcript variants and their associated miRNAs, especially miR-18a and miR-20a, as candidate stage-associated molecules in stage II/III breast cancer. Co-expressed mRNAs were identified through gene co-expression networks (WGCNA). Results: Potential MIR17HG–miR-18a/20a-mRNA regulatory axes were computationally predicted and functionally annotated to elucidate their involvement in cancer-related signaling pathways. Our findings showed that both MIR17HG splice variants were down-regulated, while their associated miRNAs (miR-18a-5p and miR-20a-5p) were overexpressed. Based on in silico prediction and functional annotation, we propose three candidate MIR17HG-centred axes: MIR17HG–miR-20a–BTG3 (linked to RNA degradation), MIR17HG–miR-18a/miR-20a–PARD6B (Hippo signaling and cell polarity), and MIR17HG–miR-20a–ZNF367 (endocytosis-related processes). Conclusion: Together, these data support MIR17HG and its associated miRNAs as candidate stage II/III breast cancer–associated ncRNA signatures and provide a framework for future functional and clinical validation studies.