oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2023-22-3-134-143oncotomsk-2586Research ArticleОБЗОРЫREVIEWSСвязь микро-РНК кластера miR-143/145 с онкогенезом: тканевой и клеточный контекстRelationship between cluster miR-143/145 micro-RNAs with oncogenesis: tissue and cellular contexthttps://orcid.org/0000-0001-7542-7285ВоропаеваЕ. И.VoropaevaE. N.

Воропаева Елена Николаевна - доктор медицинских наук, ведущий научный сотрудник лаборатории молекулярно-генетических исследований терапевтических заболеваний, НИИ терапии и профилактической медицины - филиал ФГБНУ «ФИЦ ИЦиГ СО РАН»; профессор кафедры медицинской генетики и биологии лечебного факультета, ФГБОУ ВО «НГМУ» Минздрава России.

630089, Новосибирск, ул. Б. Богаткова, 175/1; 630091, Новосибирск, ул. Красный проспект, 52

Researcher ID (WOS): A-5360-2014; Author ID (Scopus): 36020818100

Elena N. Voropaeva - MD, DSc, Leading Researcher, Laboratory of Molecular Genetic Studies of Therapeutic Diseases, Research Institute of Therapy and Preventive Medicine - Branch of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences.

175/1, Boris Bogatkov St., 630089, Novosibirsk; 52, Red Ave., 630091, Novosibirsk

Researcher ID (WOS): A-5360-2014; Author ID (Scopus): 36020818100

vena.81@mail.ruhttps://orcid.org/0000-0002-1261-5470ПоспеловаТ. И.PospelovaT. I.

Поспелова Татьяна Ивановна - доктор медицинских наук, профессор, заведующая кафедрой терапии, гематологии и трансфузиологии ФПК и ППВ.

630091, Новосибирск, ул. Красный проспект, 52

Author ID (Scopus): 7005792562

Tatiana I. Pospelova - MD, Professor, Head of the Department of Therapy, Hematology and Transfusiology, Novosibirsk State Medical University of the Ministry of Health of Russia.

52, Red Ave., 630091, Novosibirsk

Author ID (Scopus): 7005792562

https://orcid.org/0000-0002-1432-0473НестерецА. М.NesteretsA. M.

Нестерец Алина Михайловна - младший научный сотрудник лаборатории генетических и средовых детерминант жизненного цикла человека.

630089, Новосибирск, ул. Б. Богаткова, 175/1

Researcher ID (WOS): ABG-7157-2021; Author ID (Scopus): 57224450913

Alina M. Nesterets - Junior Researcher, Laboratory of Genetic and Environmental Determinants of the Human Life Cycle, Research Institute of Therapy and Preventive Medicine - Branch of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences.

175/1, Boris Bogatkov St., 630089, Novosibirsk

Researcher ID (WOS): ABG-7157-2021; Author ID (Scopus): 57224450913

https://orcid.org/0000-0002-7165-4496МаксимовВ. И.MaksimovV. N.

Максимов Владимир Николаевич - доктор медицинских наук, профессор, заведующий лабораторией молекулярно-генетических методов исследования терапевтических заболеваний, НИИ терапии и профилактической медицины - филиал ФГБНУ «ФИЦ ИЦиГ СО РАН»; доцент кафедры терапии, гематологии и трансфузиологии ФПК и ППВ, ФГБОУ ВО «НГМУ» Минздрава России.

630089, Новосибирск, ул. Б. Богаткова, 175/1; 630091, Новосибирск, ул. Красный проспект, 52

Researcher ID (WOS): H-7676-2012; Author ID (Scopus): 7202540327

Vladimir N. Maksimov - MD, Professor, Head of the Laboratory of Molecular-genetic Methods for the Study of Therapeutic Diseases, Research Institute of Therapy and Preventive Medicine - Branch of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences.

175/1, Boris Bogatkov St., 630089, Novosibirsk; 52, Red Ave., 630091, Novosibirsk

Researcher ID (WOS): H-7676-2012; Author ID (Scopus): 7202540327

НИИ терапии и профилактической медицины - филиал ФГБНУ «Федеральный исследовательский центр Институт цитологии и генетики СО РАН»; ФГБОУ ВО «Новосибирский государственный медицинский университет» Минздрава РоссииРоссияResearch Institute of Therapy and Preventive Medicine - Branch of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences; Novosibirsk State Medical University of the Ministry of Health of RussiaRussian FederationФГБОУ ВО «Новосибирский государственный медицинский университет» Минздрава РоссииРоссияNovosibirsk State Medical University of the Ministry of Health of RussiaRussian FederationНИИ терапии и профилактической медицины - филиал ФГБНУ «Федеральный исследовательский центр Институт цитологии и генетики СО РАН»РоссияResearch Institute of Therapy and Preventive Medicine - Branch of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesRussian Federation202328062023223134143Copyright © Воропаева Е.И., Поспелова Т.И., Нестерец А.М., Максимов В.И., 20232023Воропаева Е.И., Поспелова Т.И., Нестерец А.М., Максимов В.И.Voropaeva E.N., Pospelova T.I., Nesterets A.M., Maksimov V.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/2586

Цель исследования - представить современные данные о регуляции экспрессии, функции в нормальных тканях и разнонаправленной активности в онкогенезе микроРНК кластера miR-143/145, а также оценить возможности и ограничения терапевтического использования микроРНК данного кластера при злокачественных новообразованиях. Материал и методы. Проведен поиск доступных отечественных и зарубежных литературных источников, опубликованных в базах данных PubMed и РИНЦ за последние 10 лет. Найдено 427 статей, из которых 41 была включена в данный обзор. Результаты. Консервативный кластер miR-143/145 является одним из наиболее интенсивно изучаемых при опухолях. На основании результатов анализа дифференциальной экспрессии микроРНК, экспериментов in vitro в раковых клеточных линиях и in vivo в мышиных моделях опухолей было показано снижение уровня miR-143 и miR-145 при злокачественных новообразованиях эпителиального происхождения. До недавнего времени данные микроРНК считались классическими онкосупрессорами. Приведенные в обзоре данные демонстрируют, что результаты целого ряда работ, учитывающих клеточные аспекты экспрессии микроРНК, противоречат этой концепции. Для микроРНК miR-143, например, известно участие в метаболической перестройке опухоли и активации неоангиогенеза. Показано, что онкосупрессорная или проонкогенная активность miR-143 и miR-145 зависят от тканевого и клеточного контекста и могут объясняться наличием у них нескольких регулируемых мишеней, оказывающих противоположные эффекты на онкогенез. В совокупности полученные данные говорят о необходимости проявлять осторожность при выборе микроРНК описываемого кластера для экзогенной терапевтической доставки. Заключение. Дальнейшая детальная расшифровка механизмов функционирования miR-143 и miR-145 в различных типах тканей и клеток, а также идентификация новых мРНК-мишеней необходимы для лучшего понимания участия данных молекул в онкогенезе.

The purpose of the study was to present up-to-date data on the regulation of expression, function in normal tissues and multidirectional activity in the oncogenesis of miR-143/145 microRNAs cluster, as well as to evaluate the possibilities and limitations of the therapeutic use of microRNAs of this cluster in malignant neoplasms. Material and methods. The search for available domestic and foreign literary sources published in PubMed and RSCI databases over the past 10 years has been carried out. 427 articles were found, of which 41 were included in this review. Results. The conservative cluster miR-143/145 is one of the most intensively studied in tumors. Based on the results of the analysis of differential miRNA expression, in vitro experiments in cancer cell lines and in vivo in mouse tumor models, a decrease in miR-143 and miR-145 levels was shown in malignant neoplasms of epithelial origin. Until recently, these miRNAs were considered classical oncosuppressors. The data presented in the review demonstrate that the results of a number of studies taking into account the cellular aspects of microRNA expression contradict this concept. miR-143 microRNA, for example, is known to participate in the metabolic restructuring of the tumor and the activation of neoangiogenesis. It has been shown that the oncosuppressive or pro-oncogenic activity of miR-143 and miR-145 depend on the tissue and cellular context and can be explained by the presence of several regulated targets that have opposite effects on oncogenesis. Taken together, the data obtained suggest the need to exercise caution when choosing the microRNAs of the described cluster for exogenous therapeutic delivery. Conclusion. Further detailed decoding of the mechanisms of miR-143 and miR-145 functioning in various types of tissues and cells, as well as identification of new MRNA targets are necessary for a better understanding of the involvement of these molecules in oncogenesis.

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The authors declare that there are no conflicts of interest present.