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Epigenetic and Transcriptional Reprogramming in 3D Culture Models in Breast Cancer.
Laura Cecilia Flores-García1, Karla Rubio2, Eloisa Ibarra-Sierra3
1Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, San Lorenzo 290. Col. del Valle, Ciudad de Mexico C.P. 03104, Mexico.
Cancers
|December 11, 2025
Summary
Three-dimensional (3D) breast cancer models create distinct epigenetic changes, particularly in non-coding RNAs, impacting tumor cell behavior. These models offer insights into cancer biology but require standardization for reproducible research findings.
Area of Science:
- Oncology
- Cell Biology
- Epigenetics
Background:
- Breast cancer's heterogeneity complicates effective therapy development.
- Traditional 2D cell cultures fail to replicate the tumor microenvironment, limiting biological insights.
- Three-dimensional (3D) models better mimic tissue architecture and gradients, enhancing cancer research.
Purpose of the Study:
- To review the impact of 3D culture methods on epigenetic variations in breast cancer.
- To evaluate how 3D culture-induced epigenetic changes affect non-coding RNA regulation.
- To understand the influence of extracellular matrix interactions and mechanotransduction on breast cancer epigenetics.
Main Methods:
- Literature review integrating evidence from various studies on 3D culture models in breast cancer.
- Analysis of epigenetic modifications including DNA methylation, histone coding, and non-coding RNA regulation (miRNAs, lncRNAs, circRNAs).
- Examination of signaling pathways involved in mechanotransduction (e.g., integrin/FAK-ILK/Rho-YAP).
Main Results:
- 3D culture methods generate distinct epigenetic signatures, especially at the non-coding RNA level, influencing tumor cell proliferation, differentiation, and resistance.
- Histone acetylation marks are consistently reduced across different 3D culture types.
- Scaffold characteristics significantly determine the epigenetic plasticity of breast cancer cells.
Conclusions:
- 3D breast cancer models are not interchangeable and induce specific epigenetic profiles.
- Epigenetic plasticity driven by 3D culture scaffolds impacts key cancer hallmarks.
- Standardization of 3D culture parameters is crucial for reproducible and interpretable breast cancer research.
