Transcriptomics analysis reveals distinct mechanism of breast cancer stem cells regulation in mammospheres from MCF-7 and T47D cells

Hermawan, Adam and Putri, Herwandhani and Fatimah, Nurul and Prasetio, Heri Himawan (2024) Transcriptomics analysis reveals distinct mechanism of breast cancer stem cells regulation in mammospheres from MCF-7 and T47D cells. Heliyon, 10 (2): e24356. ISSN 24058440

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Abstract

Luminal A breast cancer, constituting 70 of breast cancer cases, presents a challenge due to the development of resistance and recurrence caused by breast cancer stem cells (BCSC). Luminal breast tumors are characterized by TP53 expression, a tumor suppressor gene involved in maintaining stem cell attributes in cancer. Although a previous study successfully developed mammospheres (MS) from MCF-7 (with wild-type TP53) and T47D (with mutant TP53) luminal breast cancer cells for BCSC enrichment, their transcriptomic profiles remain unclear. We aimed to elucidate the transcriptomic disparities between MS of MCF-7 and T47D cells using bioinformatics analyses of differentially expressed genes (DEGs), including the KEGG pathway, Gene Ontology (GO), drug-gene association, disease-gene association, Gene Set Enrichment Analysis (GSEA), DNA methylation analysis, correlation analysis of DEGs with immune cell infiltration, and association analysis of genes and small-molecule compounds via the Connectivity Map (CMap). Upregulated DEGs were enriched in metabolism-related KEGG pathways, whereas downregulated DEGs were enriched in the MAPK signaling pathway. Drug-gene association analysis revealed that both upregulated and downregulated DEGs were associated with fostamatinib. The KEGG pathway GSEA results indicated that the DEGs were enriched for oxidative phosphorylation, whereas the downregulated DEGs were negatively enriched for the p53 signaling pathway. Examination of DNA methylation revealed a noticeable disparity in the expression patterns of the PKM2, ERO1L, SLC6A6, EPAS1, APLP2, RPL10L, and NEDD4 genes when comparing cohorts with low- and high-risk breast cancer. Furthermore, a significant positive correlation was identified between SLC6A6 expression and macrophage presence, as well as MSN, and AKR1B1 expression and neutrophil and dentritic cell infiltration. CMap analysis unveiled SA-83851 as a potential candidate to counteract the effects of DEGs, specifically in cells harbouring mutant TP53. Further research, including in vitro and in vivo validations, is warranted to develop drugs targeting BCSCs. © 2024 The Authors

Item Type: Article
Additional Information: Cited by: 3; All Open Access, Gold Open Access, Green Open Access
Uncontrolled Keywords: Breast cancer stem cells, Transcriptomics profile, Bioinformatics, Targeted therapy
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Pharmacy
Depositing User: Yulistiarini Kumaraningrum KUMARANINGRUM
Date Deposited: 04 Nov 2024 05:51
Last Modified: 04 Nov 2024 05:51
URI: https://ir.lib.ugm.ac.id/id/eprint/10710

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