INTEGRATED EXPRESSION PROFILE OF THE MMP–TIMP–MIRNA AXIS IN BREAST CANCER CELL LINES OF DIFFERENT MOLECULAR SUBTYPES
DOI:
https://doi.org/10.15407/exp-oncology.2025.03.310Keywords:
breast cancer, MMPs, TIMPs, microRNAs, extracellular matrix remodeling, invasion, metastasisAbstract
Background. Invasion and metastasis of breast cancer (BC) critically depend on extracellular matrix (ECM) remodeling, regulated by matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs). The dysregulation of the MMP-TIMP axis, together with the post-transcriptional control by microRNAs (miRNAs), contributes to the aggressive phenotype of BC. Materials and Methods. The expression of collagenases (MMP-1, MMP-8, MMP-13), gelatinases (MMP-2, MMP-9), TIMP1—4, and selected regulatory miRNAs (miR-34a-5p, miR-100-5p, miR-132-3p, miR-145-5p, miR-155-5p, miR-200b-5p) was analyzed by immunocytochemistry and real-time PCR in 4 human BC cell lines representing different molecular subtypes (MCF‑ 7, T47D, MDA-MB-231, MDA-MB-468). Results. Distinct subtype-specific expression profiles were identified. At the mRNA level, the triple-negative BC cells showed the highest expression of collagenases (MMP1, MMP8, MMP13) and MMP9, whereas luminal BС cells of the MCF‑ 7 line exhibited the maximal MMP2 levels. At the protein level, collagenases predominated in the luminal BC cell lines (T47D, MCF‑ 7), while gelatinases were most abundant in MDA-MB-231. TIMP1 and TIMP3 transcripts were the highest in T47D, TIMP2 in MDA-MB-468 cells, while the TIMP3 expression in MDA-MB-231 cells was absent. miRNA profiling revealed a generally higher expression of miR-34a-5p, miR-100-5p, miR-132-3p, and miR-145-5p in the triple-negative BC cell lines, whereas MCF‑ 7 cells displayed the lowest levels except for miR-155-5p, the expression of which was maximal. The discrepancies between mRNA and protein levels suggest a miRNA-mediated post-transcriptional regulation, although not universally consistent across all MMPs. Conclusions. The study demonstrates that the MMP-TIMP-miRNA axis exhibits subtype-specific expression patterns in the BC cell lines. The observed heterogeneity highlights the importance of post-transcriptional regulation and suggests that integrated profiling of MMPs, TIMPs, and regulatory miRNAs may provide novel insights into the invasive potential of BC and identify candidate biomarkers for clinical validation.
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