Breast Cancer Cells Reprogram the Oncogenic lncRNAs/mRNAs Coexpression Networks in Three-Dimensional Microenvironment

Area of Science:

• * Molecular Biology
• * Cancer Research
• * Genomics

Background:

• * Traditional 2D cell cultures do not fully replicate solid tumor complexity.
• * Long non-coding RNAs (lncRNAs) roles in 3D breast cancer models remain unexplored.
• * Estrogen receptor-positive luminal B breast cancer (BT-474 cells) is a key subtype for study.

Purpose of the Study:

• * To investigate lncRNA expression and function in 3D breast cancer cultures.
• * To identify lncRNA-mRNA regulatory networks in a 3D microenvironment.
• * To compare 3D culture findings with patient data (TCGA) for luminal B breast cancer.

Main Methods:

• * Organotypic 3D cell cultures and 2D monolayer cultures of BT-474 cells.
• * Global gene expression profiling using DNA microarrays.
• * Co-expression analysis of lncRNAs and mRNAs, including comparison with TCGA datasets.

Main Results:

• * 290 lncRNAs upregulated and 183 downregulated in 3D vs. 2D cultures.
• * Hundreds of regulatory axes identified, impacting cancer hallmarks (estrogen response, proliferation, hypoxia, therapy resistance).
• * 102 lncRNA/mRNA correlations in 3D cultures mirrored TCGA patient data; LINC00847 and CTD-2566J3.1 co-expressed with survival predictors and cancer genes (FOXA1, GINS2).

Conclusions:

• * 3D breast cancer models reveal lncRNA-mRNA interactions relevant to patient tumors.
• * Identified lncRNAs and their co-expressed mRNAs may serve as biomarkers for endocrine therapy response and pathologic complete response (PCR).
• * These 3D models offer valuable preclinical tools for understanding breast cancer biology and identifying therapeutic targets.