Integrative RNA-Seq and TCGA-BRCA Analyses Highlight the Role of LINC01133 in Triple-Negative Breast Cancer

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Triple-negative breast cancer (TNBC) is highly aggressive due to lack of biomarkers and pronounced invasiveness.
• Long non-coding RNAs (lncRNAs) are implicated in cancer, with dysregulated lncRNA LINC01133 showing potential but unclear roles in TNBC.

Purpose of the Study:

• To investigate the molecular role of lncRNA LINC01133 in triple-negative breast cancer.
• To identify gene expression changes associated with LINC01133 knockout in TNBC cells.
• To explore the translational relevance of LINC01133 in patient cohorts.

Main Methods:

• Generated a TNBC cell line panel with LINC01133 knockout (Hs578T_ko) using CRISPR.
• Performed bulk RNA-sequencing (RNA-Seq) to identify differentially expressed genes (DEGs) post-knockout.
• Utilized Gene Ontology for functional enrichment analysis and TCGA-BRCA data for patient cohort comparisons.

Main Results:

• Identified 265 DEGs in LINC01133 knockout cells, enriched for pathways in cell adhesion, epithelial-mesenchymal transition (EMT), and extracellular matrix (ECM) remodeling.
• Key DEGs included ITIH5, GLUL, CACNB2, PDX1, ASPN, PTGER3, MFAP4, PI15, EPHB6, and CPA3, many linked to migration and invasion.
• Patient data analysis showed lower LINC01133 levels associated with gene expression shifts favoring ECM/EMT programs and cell adhesion modulation.

Conclusions:

• LINC01133 loss drives a transcriptomic shift towards pro-migratory and ECM remodeling signatures in TNBC.
• LINC01133 expression correlates with TNBC-associated gene programs in a concentration-dependent manner.
• LINC01133 is a potential molecule of interest for TNBC research, warranting further functional validation.