Cancer UrologyCancer UrologyОнкоурология1726-97761996-1812Publishing House ABV Press191610.17650/1726-9776-2025-21-3-190-200REVIEWSОБЗОРЫReview ArticleRole of retroelements in bladder cancer developmentВлияние ретроэлементов на развитие рака мочевого пузыряhttps://orcid.org/0000-0002-4091-382XMustafinR. N.МустафинР. Н.
Russian Federation
ruji79@mail.ruBashkir State Medical University, Ministry of Health of RussiaФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России181220252131902000903202503072025Copyright ©; 2025, Mustafin R.N.Copyright ©; 2025, Мустафин Р.Н.2025Mustafin R.N.Мустафин Р.Н.https://creativecommons.org/licenses/by/4.0https://oncourology.eco-vector.com/oncur/article/view/1916

Many studies have shown an association between increased risk of bladder cancer and hypomethylation of retroelements in human peripheral blood, as well as activation of LINE1 (long interspersed nuclear elements), HERV-K (human endogenic retrovirus K) and Alu with insertions into new genomic loci in bladder cancer tissues. Retroelement hypomethylation is accompanied by inactivation of tumor suppressor genes, such as APC, SFRP1, RASSF1A, DAPK1, RARB2, CDKN2A, TP53, RB1, CDKN2A, ERCC2, RUNX3, as well as stimulation of proto-oncogenes FGFR3, TERT, KDM6A, ELF3, PLA2G4A. According to the CancerHERVdb database, between 72.7 and 100 % of bladder cancer tissues are positive for HERV expression. Retroelements are mobile genetic elements and serve as a rich source of microRNA and long non-coding RNA genes which also participate in bladder cancer development. Analysis of the MDTE (miRNA-Derived from Transposable Elements) database allowed to describe 15 microRNAs evolved from mobile genetic elements and possessing oncogenic capabilities and 17 possessing suppressor capabilities. Long non-coding RNAs potentially can be used for targeted therapy of bladder cancer, especially inoperable metastatic drug-resistant cancer. Hereditary predisposition to bladder cancer can be explained by the fact that retroelements are located in intergene, intron and regulatory areas near most of bladder cancer-associated SNPs (single-nucleotide polymorphism). Factors of retroelement activation are aging and viral infections.

В многочисленных исследованиях был определен повышенный риск развития рака мочевого пузыря (РМП) с гипометилированием ретроэлементов в образцах периферической крови людей, а также доказана активация LINE1 (long interspersed nuclear elements, длинные диспергированные ядерные элементы), HERV-K (эндогенный ретровирус человека K) и Alu в тканях РМП с их инсерциями в новые локусы генома. Гипометилирование ретроэлементов сопровождается инактивацией генов – супрессоров опухолей, таких как APC, SFRP1, RASSF1A, DAPK1, RARB2, CDKN2A, TP53, RB1, CDKN2A, ERCC2, RUNX3, а также стимуляцией протоонкогенов FGFR3, TERT, KDM6A, ELF3, PLA2G4A. Согласно базе данных CancerHERVdb, от 72,7 до 100 % тканей РМП позитивны на экспрессию HERV. Ретроэлементы относятся к мобильным генетическим элементам, которые являются богатыми источниками генов микроРНК и длинных некодирующих РНК, роль которых в развитии РМП также описана. Анализ базы данных MDTE (miRNA-derived from transposable elements) позволил описать 15 произошедших от мобильных генетических элементов микроРНК с онкогенными свойствами и 17 со свойствами супрессоров опухолей. Использование данных некодирующих РНК предполагается для таргетной терапии РМП, особенно в отношении неоперабельного метастазирующего фармакорезистентного рака. Наследственную предрасположенность к развитию РМП можно объяснить локализацией ретроэлементов в межгенных, интронных и регуляторных областях, где расположено большинство SNP (single-nucleotide polymorphism, однонуклеотидный полиморфизм), ассоциированных с РМП. Факторами активации ретроэлементов при РМП являются старение и вирусные инфекции.

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