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LncRNA-Based Classification of Triple Negative Breast Cancer Revealed Inherent Tumor Heterogeneity and Vulnerabilities
Triple negative breast cancer (TNBC) represents a diverse group of cancers based on their gene expression profiles. While the current mRNA-based classification of TNBC has contributed to our understanding of the heterogeneity of this disease, whether such heterogeneity can be resolved employing a lo...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326727/ https://www.ncbi.nlm.nih.gov/pubmed/35893227 http://dx.doi.org/10.3390/ncrna8040044 |
Sumario: | Triple negative breast cancer (TNBC) represents a diverse group of cancers based on their gene expression profiles. While the current mRNA-based classification of TNBC has contributed to our understanding of the heterogeneity of this disease, whether such heterogeneity can be resolved employing a long noncoding RNA (lncRNA) transcriptome has not been established thus far. Herein, we used iterative clustering and guide-gene selection (ICGS) and uniform manifold approximation and projection (UMAP) dimensionality reduction analysis on a large cohort of TNBC transcriptomic data (TNBC = 360, normal = 88) and classified TNBC into four main clusters: LINC00511-enriched, LINC00393-enriched, FIRRE-enriched, and normal tissue-like. Delving into associated gene expression profiles revealed remarkable differences in canonical, casual, upstream, and functional categories among different lncRNA-derived TNBC clusters, suggesting functional consequences for altered lncRNA expression. Correlation and survival analysis comparing mRNA- and lncRNA-based clustering revealed similarities and differences between the two classification approaches. To provide insight into the potential role of the identified lncRNAs in TNBC biology, CRISPR-Cas9 mediated LINC00511 promoter deletion reduced colony formation and enhanced the sensitivity of TNBC cells to paclitaxel, suggesting a role for LINC00511 in conferring tumorigenicity and resistance to therapy. Our data revealed a novel lncRNA-based classification of TNBC and suggested their potential utilization as disease biomarkers and therapeutic targets. |
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