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• W3004511541 abstract "Breast cancer has the highest incidence rate of all cancers in women worldwide. This cancer usually has an excellent prognosis with an 80% of survival rates. Although women under 35 years of age represent 3-4% of the total cases diagnosed, their tumours are characterized by being larger, more proliferative, and with an overrepresentation of more aggressive subtypes and worse prognosis. Neoplastic transformations are associated with alterations in DNA methylation, including both global hypomethylation and gene-specific hypermethylation. On the other hand, miRNAs are small non-coding molecules of RNA with an important role in the regulation of gene expression as part of the epigenetic machinery, but they can also be epigenetically modified by DNA methylation. One of the aims of the present work is to establish a miRNA expression profile characteristic of women younger than 35 years using breast cancer cell lines commercially available and identify a good cellular model for the study of breast cancer in young women. Moreover, we want to evaluate methylation differences (global methylation and methylation of genes encoding miRNAs) between young and old women with breast cancer and their DNA epigenetic age. The miRNA expression profile was carried out using Affymetrix Genechip miRNA 2.0 microarray that includes 1 100 human miRNAs whose expression was analysed in 5 breast cancer cell lines: HCC1500, HCC1937, MDA-MB-231, MDA-MB-468 and HCC1806. Additionally, DNA methylation studies were performed using the Illumina Human Methylation 850k Beadchip, analysing 21 samples from young women and 13 from older counterparts. We identified a different miRNA expression profile between breast cancer cell lines from old and young women that was compared with the miRNA profile identified in breast cancer patients. Our study has allowed us to characterize the two breast cancer cell lines, HCC1937 and HCC1500, both from young women, as good models for the study of breast cancer in patients younger than 35 years. On the other hand, we observed a different methylation profile between age groups, also in regulatory regions of gene encoding miRNAs. Specifically, our results showed a global hypomethylation in tumours from young women as well as a specific hypermethylation, centred mainly in open-sea regions of the genome in younger patients. We also found an acceleration in the epigenetic age of tumours from young women that could be increasing their genome instability. HDAC5 was significantly hypomethylated and overexpressed in young women with breast cancer. Functional studies with cell lines showed a significant reduction in the proliferation and migration when the HDAC5 gene was inhibited by the HDACi inhibitor, LMK-235. This inhibition was evident in the triple-negative molecular subtypes of both age groups. The hypomethylation of miR-124-2 was associated with poor survival in patients with breast cancer younger than 35 years old compared to older women. The differences observed in young patients with breast cancer in our work and others, reinforce the hypothesis that breast cancer that occurs in very young women has potentially unique, aggressive and complex biological features and more efforts should be done to achieve a more personalized treatment." @default.
• W3004511541 created "2020-02-14" @default.
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• W3004511541 date "2019-01-01" @default.
• W3004511541 modified "2023-09-24" @default.
• W3004511541 title "Study of the epi- / genomic dysregulation of breast cancer in women under 35 years and evaluation of cellular models" @default.
• W3004511541 hasPublicationYear "2019" @default.
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