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Background: In breast cancer, the epithelial to mesenchyme transition (EMT) is associated to tumour dissemination, drug resistance and high relapse risks. It is partly controlled by epigenetic modifications such as histone acetylation and methylation. The identification of genes involved in these reversible modifications represents an interesting therapeutic strategy to fight metastatic disease by inducing mesenchymal cell differentiation to an epithelial phenotype.
Methods: We designed a siRNA library based on chromatin modification-related to functional domains and screened it in the mesenchymal breast cancer cell line MDA-MB-231. The mesenchyme to epithelium transition (MET) activation was studied by following human E-CADHERIN (E-CAD) induction, a specific MET marker, and cell morphology. Candidate genes were validated by studying the expression of several differential marker genes and their impact on cell migration.
Results: The screen led to the identification of 70 gene candidates among which some are described to be, directly or indirectly, involved in EMT like ZEB1, G9a, SMAD5 and SMARCD3. We also identified the DOT1L as involved in EMT regulation in MDA-MB-231. Moreover, for the first time, KAT5 gene was linked to the maintenance of the mesenchymal phenotype.
Conclusions: A multi-parametric RNAi screening approach was developed to identify new EMT regulators such as KAT5 in the triple negative breast cancer cell line MDA-MB-231.
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http://dx.doi.org/10.1186/s12885-016-2683-5 | DOI Listing |
JCO Glob Oncol
May 2025
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Purpose: Breast cancer remains a significant public health challenge globally, as well as in India, where it is the most frequently diagnosed cancer in females. Significant disparities in incidence, mortality, and access to health care across India's sociodemographically diverse population highlight the need for increased awareness, policy reform, and research.
Design: This review consolidates data from national cancer registries, global cancer databases, and institutional findings from a tertiary care center to examine the epidemiology, clinical challenges, and management gaps specific to India.
J Med Screen
September 2025
The Cancer Registry of Norway, Department of Screening programs, Norwegian Institute of Public Health, Oslo, Norway.
ObjectiveTo study the implications of implementing artificial intelligence (AI) as a decision support tool in the Norwegian breast cancer screening program concerning cost-effectiveness and time savings for radiologists.MethodsIn a decision tree model using recent data from AI vendors and the Cancer Registry of Norway, and assuming equal effectiveness of radiologists plus AI compared to standard practice, we simulated costs, effects and radiologist person-years over the next 20 years under different scenarios: 1) Assuming a €1 additional running cost of AI instead of the €3 assumed in the base case, 2) varying the AI-score thresholds for single vs. double readings, 3) varying the consensus and recall rates, and 4) reductions in the interval cancer rate compared to standard practice.
View Article and Find Full Text PDFJ Natl Cancer Inst
September 2025
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States.
Background: Among childhood cancer survivors, germline rare variants in autosomal dominant cancer susceptibility genes (AD CSGs) could increase subsequent neoplasm (SNs) risks, but risks for rarer SNs and by age at onset are not well understood.
Methods: We pooled the Childhood Cancer Survivor Study and St Jude Lifetime Cohort (median follow-up = 29.7 years, range 7.
PLoS One
September 2025
Institute of Computational Science and Technology, Guangzhou University, Guangzhou, China.
MicroRNAs (miRNAs) are critical regulators of gene expression in cancer biology, yet their spatial dynamics within tumor microenvironments (TMEs) remain underexplored due to technical limitations in current spatial transcriptomics (ST) technologies. To address this gap, we present STmiR, a novel XGBoost-based framework for spatially resolved miRNA activity prediction. STmiR integrates bulk RNA-seq data (TCGA and CCLE) with spatial transcriptomics profiles to model nonlinear miRNA-mRNA interactions, achieving high predictive accuracy (Spearman's ρ > 0.
View Article and Find Full Text PDFPLoS One
September 2025
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Objective: This study employs integrated network toxicology and molecular docking to investigate the molecular basis underlying 4-nonylphenol (4-NP)-mediated enhancement of breast cancer susceptibility.
Methods: We integrated data from multiple databases, including ChEMBL, STITCH, Swiss Target Prediction, GeneCards, OMIM and TTD. Core compound-disease-associated target genes were identified through Protein-Protein Interaction (PPI) network analysis.