ONCOLOGY / CLINICAL RESEARCH
miRNA-mediated regulation of extracellular matrix dynamics across breast cancer subtypes
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1
Department of Plastic Surgery, Faculty of Medicine, Academia of Silesia, Katowice, Poland
2
Department of Plastic and Reconstructive Surgery, Hospital for Minimally Invasive and Reconstructive Surgery in Bielsko-Biala, Bielsko-Biala, Poland
3
Department of Medical and Health Sciences, Collegium Medicum, WSB University, Dabrowa Gornicza, Poland
4
Independent Researcher, Wloclawek, Poland
5
Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski University in Krakow, Krakow, Poland
6
Department of Gynecology and Obstetrics, TOMMED Specjalisci od Zdrowia, Katowice, Poland
7
Chalcarz Clinic-Aesthetic Surgery, Aesthetic Medicine, Poznan, Poland
8
Bieńkowski Medical Center-Plastic Surgery, Bydgoszcz, Poland
9
New Medical Techniques Specjalist Hospital of St. Family in Rudna Mała, Rzeszow, Poland
Submission date: 2025-02-06
Final revision date: 2025-05-18
Acceptance date: 2025-05-30
Online publication date: 2025-07-10
Corresponding author
Tomasz Sirek
Department of Plastic Surgery, Faculty of Medicine, Academy of Silesia, 40-555, Katowice, Poland
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Interactions between extracellular signals and the extracellular matrix (ECM) influence cellular phenotype and molecular functions, affecting proliferation, differentiation, adhesion, apoptosis, and migration. Deregulation of ECM remodeling contributes to the development of diseases, including breast cancer. The study was aimed to identify microRNAs (miRNAs) that may regulate the activity of genes involved in ECM remodeling and focal adhesion across five breast cancer subtypes in Polish women.
Material and methods:
The study enrolled patients representing five breast cancer subtypes: 130 luminal A, 100 HER2-negative luminal B, 96 HER2-positive luminal B, 36 non-luminal HER2-positive, 43 triple-negative breast cancer (TNBC) cases. Cancer tissue samples were collected during surgery along with healthy tissue margins (control group). The expression profiles of genes associated with ECM remodeling and focal adhesion were evaluated with mRNA microarrays and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Protein expression was assessed using enzyme-linked immunosorbent assay (ELISA). miRNA detection and target prediction were performed using miRNA microarrays.
Results:
Overexpression of COL1A1, FN1, ITGB1, and THBS1 may be associated with reduced levels of miR-129, miR-432, miR-124, and miR-384, respectively. Decreased COL6A6 expression may result from increased activity of miR-1246. Additionally, the study revealed increased levels of COL1A2, COMP, and SPP1 with reduced activity of RELN, across all five breast cancer subtypes.
Conclusions:
This is the first study to comprehensively analyze miRNA-mediated regulation of ECM-related genes across five breast cancer subtypes in a Polish cohort. Overexpression of COL1A1, FN1, and ITGB1 is linked to reduced levels of specific miRNAs, while decreased COL6A6 expression is associated with increased miR-1246 activity.
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