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 level 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 breast cancer. Hypermethylation of all seven lncRNA genes was revealed, and hypermethylation of HAND2-AS1, KCNK15-AS1, MAGI2-AS3 and PLUT was detected by us 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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About the authors

E. A. Filippova

Institute of General Pathology and Pathophysiology

Author for correspondence.
Email: p.lenyxa@yandex.ru
Russian Federation, Moscow, 125315

V. I. Loginov

Institute of General Pathology and Pathophysiology

Email: p.lenyxa@yandex.ru
Russian Federation, Moscow, 125315

S. S. Lukina

Institute of General Pathology and Pathophysiology

Email: p.lenyxa@yandex.ru
Russian Federation, Moscow, 125315

A. M. Burdennyy

Institute of General Pathology and Pathophysiology

Email: p.lenyxa@yandex.ru
Russian Federation, Moscow, 125315

I. V. Pronina

Institute of General Pathology and Pathophysiology

Email: p.lenyxa@yandex.ru
Russian Federation, Moscow, 125315

T. P. Kazubskaya

Blokhin National Medical Research Center of Oncology

Email: p.lenyxa@yandex.ru
Russian Federation, Moscow, 115478

E. A. Braga

Institute of General Pathology and Pathophysiology

Email: p.lenyxa@yandex.ru
Russian Federation, Moscow, 125315

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2. Fig. 1. Methylation level of lncRNA genes MEG3, SEMA3B-AS1, HAND2-AS1, KCNK15-AS1, ZNF667-AS1, MAGI2-AS3 and PLUT in breast tumor samples and paired normal tissues. The upper and lower boundaries of the rectangles in the diagrams correspond to Q1 and Q3 (50% of the values fall inside the rectangle). The line inside the rectangle corresponds to the median. The lines above and below the rectangles indicate a “fence” located at a distance of 1.5 interquartile distances (Q1–Q3) from the lower and upper boundaries of the “box”.

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3. Fig. 2. Level of methylation of lncRNA genes MEG3, SEMA3B-AS1, HAND2-AS1, KCNK15-AS1, ZNF667-AS1, MAGI2-AS3 and PLUT in samples of breast tumors at the late stage of breast cancer (III) compared with early stages of breast cancer (I– II) and normal tissues.

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4. Fig. 3. Methylation level of lncRNA genes MEG3, SEMA3B-AS1, HAND2-AS1, KCNK15-AS1, ZNF667-AS1, MAGI2-AS3 and PLUT in breast tumor samples with metastases (N1–N3) and without metastases (N0).

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5. Fig. 4. Level of methylation of the lncRNA PLUT gene in samples of breast tumors that do not express progesterone receptors (PR-) and estrogen receptors (ER-) and expressing progesterone receptors (PR+) and estrogen receptors (ER+).

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