MFUM-BrTNBC-1, a Newly Established Patient-Derived Triple-Negative Breast Cancer Cell Line: Molecular Characterisation, Genetic Stability, and Comprehensive Comparison with Commercial Breast Cancer Cell Lines

Skok, Kristijan; Gradišnik, Lidija; Čelešnik, Helena; Milojević, Marko; Potočnik, Uroš; Jezernik, Gregor; Gorenjak, Mario; Sobočan, Monika; Takač, Iztok; Kavalar, Rajko; Maver, Uroš

doi:10.3390/cells11010117

Cited by 7 publications

(3 citation statements)

References 97 publications

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“…The invasive nature of MDA‐MB‐231 cells, which has been reported in numerous studies causes nuclear deformities such as grooves, invagination, lobes, and semicircular contour, allowing greater amount Pdot to penetrate into cell nuclei thus nucleus‐staining property of small molecule DAPI is achieved by a fluorescent polyelectrolyte selectively. [ 44,49–51 ] This feature can be attributed to the more nuclear penetration of Pdot in MDA‐MB‐231 cells compared to MCF‐7.…”

Section: Resultsmentioning

confidence: 99%

The Soft Nanodots as Fluorescent Probes for Cell Imaging: Analysis of Cell and Spheroid Penetration Behavior of Single Chain Polymer Dots

Yucel,

Onbas,

Arslan Yildiz

et al. 2024

Macromolecular Bioscience

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This study describes the formation, size control and penetration behavior of polymer nano dots (Pdots) consisting of single or few chain polythiophene based conjugated polyelectrolytes (CPEs) via nanophase separation between good solvent and poor solvent of CPE. Though the chain singularity may be associated with dilution nanophase separation suggests that molecules of a good solvent create a thermodynamically driven solvation layer surrounding the CPEs and thereby separating the single chains even in their poor solvents. This statement is therefore corroborated with emission intensity/lifetime, particle size, and scattering intensity of polyelectrolyte in good and poor solvents. Regarding the augmented features, Pdots are implemented into cell imaging studies to understand the nuclear penetration and to differentiate the invasive characteristics of breast cancer cells. The python based RGB imaging depicts that Pdots have more nuclear penetration ability in triple negative breast cancer cells due to the different nuclear morphology in shape and composition and have penetrated cell membrane as well as extracellular matrix in spheroid models. The current Pdot protocol and its utilization in cancer cell imaging are holding great promise for gene/drug delivery to target cancer cells by explicitly achieving the very first priority of nuclear intake.This article is protected by copyright. All rights reserved

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Section: Resultsmentioning

confidence: 99%

The Soft Nanodots as Fluorescent Probes for Cell Imaging: Analysis of Cell and Spheroid Penetration Behavior of Single Chain Polymer Dots

Yucel,

Onbas,

Arslan Yildiz

et al. 2024

Macromolecular Bioscience

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“…Using TCGA BC RNA expression data (n = 1084), we observed a highly signi cant positive correlation between KDM7A-DT and KRT7 mRNA levels (r = 0.47, p < 1.00E-56, Spearman; Figure 5G) but a highly signi cant negative correlation between KDM7A-DT and GATA3 mRNA levels (r = -0.48, p < 1.00E-56, Spearman; Figure 5H). KRT7 overexpression is a reliable marker of the BL BC subtype (55,69,70). Low GATA3 mRNA expression is associated with the BL subtype of BC and poor patient prognosis (71).…”

Section: Kdm7a-dt Is Overexpressed In the Aggressive Bl Bc Subtypementioning

confidence: 99%

TP53 mutation–associated and copy number–dependent KDM7A-DT expression affects DNA repair and promotes invasive breast cancer progression

Giannakakis¹,

Tsifintaris

Gouzouasis

et al. 2022

Preprint

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Background: Recent characterisation of stress-induced promoter-associated antisense lncRNAs (si-paancRNAs) suggests that these lncRNAs modulate transcription, cellular responses to oxidative, metabolic and genotoxic stress, and may be part of the pathways critical in cancer. KDM7A divergent transcribed (KDM7A-DT) is among the top overexpressed genes encoded by such lncRNAs. The mechanisms leading to aberrant KDM7A-DT transcription, transcript biogenesis, and downstream functions of KDM7A-DT isoforms in breast cancer (BC) types and subtypes have not been studied. Methods: Cell line models, biochemistry methods and microarrays experiments for overexpression and knockdown of KDM7A-DT were used. Next, integration of experimental models, bioinformatics, and massive BRCA patient metadata analyses were performed to investigate the mechanisms and functions of KDM7A-DT.Results: The stable KDM7A-DT overexpression in non-malignant cells upregulates p53, CDKN1A, and γH2AX signalling, resulting in a prolonged cell growth retardation phenotype and preferential depletion of epithelial-to-mesenchymal transition (EMT) pathway–associated tumour suppressor genes. Importantly, KDM7A-DT induction by acute oxidative stress of semi-transformed fibroblasts is p53-dependent. According to BC clinical metadata, KDM7A-DT is overexpressed in poor survival basal-like BC (BLBC) subtype. The KDM7A-DT overexpression is associated with the overexpression of the TP53-missense mutated gene and KDM7A-DT full-length copy number amplification. KDM7A-DT overexpression affects DNA repair via the non-homologous end-joining (NHEJ) pathway, inhibits tumor suppressors involved in EMT, induces pro-oncogenic metabolic changes, and correlates with histologic grades, aneuploidy, hypoxia, cancer-associated proteins, clinical and molecular markers.Conclusion: KDM7A-DT is the TP53 mutation–associated and copy number–dependent pro-oncogene si-paancRNAs that contributes to genome instability, initiation, progression, invasiveness, and BLBC outcomes.

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“…Using TCGA BC RNA expression data (n = 1084), we observed a highly signi cant positive correlation between KDM7A-DT and KRT7 mRNA levels (r = 0.47, p < 1.00E-56, Spearman; Figure 5G) but a highly signi cant negative correlation between KDM7A-DT and GATA3 mRNA levels (r = -0.48, p < 1.00E-56, Spearman; Figure 5H). KRT7 overexpression is a reliable marker of the BL BC subtype (55, 69,70). Low GATA3 mRNA expression is associated with the BL subtype of BC and poor patient prognosis (71).…”

Section: Kdm7a-dt Is Overexpressed In the Aggressive Bl Bc Subtypementioning

confidence: 99%

TP53 mutation–associated and copy number–dependent KDM7A-DT expression affects DNA repair and promotes invasive breast cancer progression

Giannakakis

Tsifintaris

Triantafyllou

et al. 2022

Preprint

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Background Recent characterization of stress-induced promoter-associated antisense lncRNAs (si-paancRNAs) suggests that they modulate transcription and cellular responses to oxidative, metabolic and genotoxic stress and may participate in critical cancer pathways. KDM7A divergent transcript (KDM7A-DT) is one of such stress-induced lncRNAs, whose expression is found deregulated in breast cancer (BC). The mechanisms leading to aberrant KDM7A-DT transcription, biogenesis, and downstream functions in BC types and subtypes have not been studied. Methods Cell lines, biochemical methods, and profiling experiments were used for KDM7A-DT overexpression and knockdown. Integration of experimental models, bioinformatics, and massive BRCA patient metadata analyses were performed to investigate the mechanisms and functions of KDM7A-DT. Results Stable KDM7A-DT overexpression in nonmalignant cells upregulates p53, CDKN1A, and γH2AX signaling, resulting in a prolonged cell growth retardation phenotype. Importantly, KDM7A-DT induction by acute oxidative stress in semi-transformed fibroblasts is p53-dependent. According to BC clinical metadata, KDM7A-DT gene alterations are preferentially associated with TP53 missense mutations and highly aggressive, invasive, basal-like (BL) subtype BC poor outcomes. Overall, KDM7A-DT affects DNA repair via the nonhomologous end-joining pathway, inhibits tumor suppressors involved in epithelial-to-mesenchymal transition, induces oncogenic metabolic changes and G2/M checkpoint arrest, and correlates with histology, aneuploidy, hypoxia and BC-associated proteins. Conclusion KDM7A-DT is a TP53 mutation–associated and copy number–dependent pro-oncogene si-paancRNA that contributes to genome instability and modulates BC initiation, progression, invasiveness and outcomes.

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MFUM-BrTNBC-1, a Newly Established Patient-Derived Triple-Negative Breast Cancer Cell Line: Molecular Characterisation, Genetic Stability, and Comprehensive Comparison with Commercial Breast Cancer Cell Lines

Cited by 7 publications

References 97 publications

The Soft Nanodots as Fluorescent Probes for Cell Imaging: Analysis of Cell and Spheroid Penetration Behavior of Single Chain Polymer Dots

The Soft Nanodots as Fluorescent Probes for Cell Imaging: Analysis of Cell and Spheroid Penetration Behavior of Single Chain Polymer Dots

TP53 mutation–associated and copy number–dependent KDM7A-DT expression affects DNA repair and promotes invasive breast cancer progression

TP53 mutation–associated and copy number–dependent KDM7A-DT expression affects DNA repair and promotes invasive breast cancer progression

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