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A Group of New Hypermethylated Long Non-Coding RNA Genes Associated with the Development and Progression of Breast Cancer

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Abstract—Breast cancer is the most common type of cancer among women. The study of the mechanisms of metastasis, the main cause of death from breast cancer, as well as the search for new markers for early diagnosis and prognosis of breast cancer, is an extremely topical issue. New perspectives in the diagnosis and treatment of breast cancer are opened by the mechanisms of gene regulation involving non-coding RNAs, in particular, long non-coding RNAs (lncRNAs). In this work, we analyzed the methylation levels of seven lncRNA genes (MEG3, SEMA3B-AS1, HAND2-AS1, KCNK15-AS1, ZNF667-AS1, MAGI2-AS3, and PLUT) by quantitative methyl-specific PCR on a set of 79 paired (tumor/normal) samples of breast cancer. Hypermethylation of all seven lncRNA genes was revealed, and hypermethylation of HAND2-AS1, KCNK15-AS1, MAGI2-AS3, and PLUT was detected in breast cancer for the first time. It was found that the level of methylation of the studied lncRNA genes correlated statistically significantly with the stage of the tumor process, the size of the tumor, and the presence of metastases in the lymph nodes. Thus, methylation of the seven studied lncRNA genes is associated with the development and progression of breast cancer, and these genes can be useful as potential markers in the diagnosis and prognosis of breast cancer.

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Funding

The work was carried out at the expense of the Russian Science Foundation (grant No. 22-75-00132).

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Correspondence to E. A. Filippova.

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All procedures performed in this work are in accordance with the ethical standards of the Institutional Research Ethics Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was considered and approved by the local Ethics Committee of the Institute of General Pathology and Pathophysiology (protocols No. 1 dated March 3, 2022 and No. 4 dated August 31, 2023). All patients received written informed consent to participate in the work.

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Filippova, E.A., Loginov, V.I., Lukina, S.S. et al. A Group of New Hypermethylated Long Non-Coding RNA Genes Associated with the Development and Progression of Breast Cancer. Mol Biol 58, 71–80 (2024). https://doi.org/10.1134/S0026893324010035

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