Tumors of female reproductive systemTumors of female reproductive systemОпухоли женской репродуктивной системы1994-40981999-8627Publishing House ABV Press44310.17650/1994-4098-2015-11-3-15-21MAMMOLOGY. TOPICAL ISSUEМАММОЛОГИЯ. АКТУАЛЬНАЯ ТЕМАmiR-21 and miR-155 in the regulation of TGF-β1/SMAD signaling pathway of the line breast cancer cells with different metastatic potentialmiR-21 и miR-155 в регуляции TGF-β1/SMAD-сигнального пути в линии клеток рака молочной железы с различным метастатическим потенциаломNikiphorovaZ. N.НикифороваЗ. Н.
Russian Federation
zojanik@rambler.ruKudryavtsevI. A.КудрявцевИ. А.
Russian Federation
ShevchenkoV. Е.ШевченкоВ. Е.
Russian Federation
N.N. Blokhin Russian Cancer Research CenterФГБНУ «Российский онкологический научный центр им. Н.Н. Блохина»24 Kashirskoe Shosse, Moscow, 115201, RussiaРоссия, 115201, Москва, Каширское шоссе, 241609201511315211509201515092015https://ojrs.abvpress.ru/ojrs/article/view/443

Breast cancer (ВС) is the most common form of cancer, leading to high mortality rates among women worldwide. Metastasis is the main cause of fatal outcomes in ВС. In this regard, of particular interest takes the study of molecular mechanisms of epithelial-mesenchymal transition (EMT). In the EMT processes involved in TGF-β1/SMAD-signaling pathway through the regulation of which can affect the processes of metastasis in ВС. 

In this study we have analyzed changes of mRNA expression of the mRNA SMADs, miR-21, and miR-155 of the tumor ВС cells with different metastatic potential MCF-7, BT-474, ZR-75-1. High expression of miR-21 was detected in all the tumor cell lines (MCF-7, ZR-75-1 and BT-474). In the ВС cell lines, the expression level of miR-155 was significantly lower than that of miR-21. Analysis of mRNA expression has clearly shown impairments of intracellular mechanisms of regulation of SMAD2, SMAD4, SMAD7 in ВС. 

Investigated the correlation of expression of miR-21 and miR-155 regulation of SMADs in TGF-β1/SMAD signaling pathway in three carcinomas lines of the human breast with different metastatic potential (MCF-7, ZR-75-1, BT-474). A significant inverse correlation was observed between SMAD4 and miR-155 in MCF-7 cells. Inverse correlation between the expression of SMAD2, SMAD4, SMAD7 and miR-155; miR21 was found in the BT-474 cells. 

The results obtained in this study showed that miR-21 and miR-155 regulate activity of several genes SMAD2, SMAD4, SMAD7 in the tumor cell ZR-75-1 and on some genes they exhibited a cumulative effect. It should be noted that the miR-155 and miR-21 in various degrees influenced the expression of SMAD2, SMAD4, SMAD7, blocking the work of these genes and, thereby exacerbating the progression and degree of malignancy of ВС cells human; in some cases their effects on individual genes were cumulative. 

Рак молочной железы (РМЖ) является одной из основных онкопатологий среди женщин. Метастазы – главная причина фатальных исходов при РМЖ. В этой связи особый интерес приобретает изучение молекулярных механизмов эпителиально-мезенхимального перехода (ЭМП). В механизмы ЭМП вовлечен TGF-β1/SMAD-сигнальный путь, через регуляцию которого можно воздействовать на процессы метастазирования при РМЖ. В данной работе была изучена экспрессия мРНК семейства SMAD, miR-21 и miR-155. Экспрессия miR-21 в опухолевых клетках линий MCF-7, ZR-75-1, BT-474 была увеличена. Уровень экспрессии miR-155 был значительно ниже уровня экспрессии miR-21. В опухолевых клетках РМЖ внутриклеточные механизмы регуляции SMAD2, SMAD4, SMAD7 были нарушены. 

Исследована корреляционная связь экспрессии miR-21 и miR-155 с регуляцией SMADs в TGF-β1/SMAD-сигнальном пути в 3 линиях карцином молочной железы человека c различным метастатическим потенциалом (MCF-7, ZR-75-1, BT-474). В клеточной линии MCF-7 значимая обратная корреляция наблюдалась между SMAD4 и miR-155. В клеточной линии BT-474 – между уровнями экспрессии SMAD2, SMAD4, SMAD7 и miR-155, miR-21. В клеточной линии ZR-75-1 была выявлена корреляция экспрессии мРНК SMAD2, SMAD4, SMAD7 как с miR-155, так и с miR-21. Результаты работы свидетельствуют о том, что miR-155 и miR-21 в различной степени влияли на экспрессию SMAD2, SMAD4, SMAD7, блокируя работу этих генов и усиливая прогрессию и степень злокачественности клеток РМЖ человека, а в некоторых случаях их эффект был кумулятивным. 

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