Молекулярная биология, 2022, T. 56, № 3, стр. 516-520

MiR-485-3p и miR-4728-5p как супрессоры опухолевого роста в патогенезе колоректального рака

T. Gurer a*, A. Aytekin b**, E. Caki a, S. Gezici c

a Department of Biology, Faculty of Science and Literature, Gaziantep University
27310 Gaziantep, Turkey

b Department of General Surgery, Faculty of Medicine, Gaziantep University
27310 Gaziantep, Turkey

c Department of Medical Biology and Genetics, Faculty Medicine, Gaziantep University
27310 Gaziantep, Turkey

* E-mail: turkanayte@hotmail.com
** E-mail: taytekin@gantep.edu.tr

Поступила в редакцию 05.09.2021
После доработки 22.09.2021
Принята к публикации 24.09.2021

Аннотация

MикрoРНК – класс малых некодирующих РНК, главные функции которых связаны с развитием и прогрессией колоректального рака (CRC), где они действуют как супрессоры опухолевого роста или онкогены. Изучена роль микроРНК miR-485-3p и miR-4728-5p в патогенезе CRC. Образцы опухолей и прилегающих морфологически нормальных тканей получены от 59 больных CRC (37 образцов рака толстой кишки и 22 образца рака прямой кишки). Профили экспрессии miR-485-3p и miR-4728-5p определяли, используя количественную обратную транскрипцию с последующей полимеразной цепной реакцией. Регуляторные сети факторов транскрипции (TF), связанных с микроРНК, конструировали с использованием TransmiR v2.0. Регулируемые TF гены-мишени определяли, используя Human.mirFFL.DB и TRRUST v2.0, функциональную аннотацию и анализ обогащения с помощью DIANA-mirPath v3.0 и -Tarbase v7.0. Показано значительное снижение уровней экспрессии и miR-485-3p, и miR-4728-5p в тканях CRC (кратность изменений составила 0.42 ± 0.70 и 0.59 ± 1.06 соответственно; p = 0.000). С другой стороны, более низкие уровни экспрессии miR-485-3p выявлены и в прямой, и в толстой кишке. Более того, снижение уровней экспрессии miR-4728-5p коррелировало с увеличением возраста. Эти различия были статистически незначимыми (FDR-значения p составили 0.126 и 0.168 соответственно). С помощью биоинформатического анализа идентифицированы TF, связанные с miR-485-3p и miR-4728-5p. Некоторые из этих TF, а именно, AR, CREB1, CEBPB, FOXA1, GTF2I, MAZ, NCOR2, NFIC, NRF1, SIN3A, SREBF1, SREBF2, TP53 и YY1, по-видимому, ассоциированные с CRC, выбраны для конструирования потенциальных мишеней сетей микроРНК-TF-ген для ранней диагностики и терапии CRC. Анализ обогащения путей показывает, что сигнальный путь Hippo строго регулируется miR-485-3p. Предполагается, что снижение экспрессии miR-485-3p и miR-4728-5p может быть ассоциировано с развитием CRC.

Ключевые слова: колоректальный рак, микроРНК ОТ-ПЦР, опухолевые супрессоры, факторы транскрипции, биоинформатика

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Supplementary Table 1. List of qRT-PCR results