Cancer UrologyCancer UrologyОнкоурология1726-97761996-1812Publishing House ABV Press161510.17650/1726-9776-2022-18-4-99-107REVIEWSОБЗОРЫThe probable role of retroelements in the development of Wilms’ tumor in chromosomal syndromesВероятная роль ретроэлементов в развитии опухоли Вильмса при хромосомных синдромахhttps://orcid.org/0000-0002-4091-382X4810-2534MustafinR. N.МустафинР. Н.
Russian Federation

Rustam Nailevich Mustafin

3 Lenina St., Ufa 450008

Рустам Наилевич Мустафин - доцент кафедры медицинской генетики и фундаментальной медицины, кандидат биологических наук

450008 Уфа, ул. Ленина, 3

ruji79@mail.ruBashkir State Medical University, Ministry of Health of RussiaФГБОУ ВО "Башкирский государственный медицинский университет" Минздрава России031220221849910708092022221220222022https://oncourology.abvpress.ru/oncur/article/view/1615

The review article analyzes the data accumulated in the literature on the association of Wilms’ tumor with chromosomal syndromes and searches for possible causes of this phenomenon. In 10 % of all cases, nephroblastoma is represented by a hereditary tumor syndrome due to germline mutations in suppressor genes, mainly in the WT1 gene, less often in WT2, WTX, CTNNB1, TP53. These genes are associated with retroelements that play a role in the development of Wilms’ tumor, promoting carcinogenesis, causing genome instability. LINE-1 retroelement is a negative regulator of WT1 expression, while suppressor genes are characterized by suppression of retroelement activity. Part of the pathogenesis of Perlman, Beckwith-Wiedemann, WAGR, and trisomy 18 syndromes caused by germline microdeletions is the activation of retroelements that promote somatic chromosomal rearrangements, including deletions, insertions, and translocations, which are characteristic of sporadic Wilms’ tumor. Long noncoding RNAs and microRNAs are formed from retroelements during evolution or directly during the processing of their transcripts. At the same time, long noncoding RNAs affect the development of Wilms’ tumor by various mechanisms: due to the effect on ferroptosis (lncRNA AC007406.1, AC005208.1, LINC01770, DLGAP1-AS2, AP002761.4, STPG3-AS1, AC129507.1, AC234772.2, LINC02447, AC009570.1, ZBTB20-AS1 and LINC01179), Wnt/β-catenin signaling pathways (HOTAIR, MEG3), apoptosis (HAGLROS), regulation of expression of specific miRNAs (SNHG6, MEG8, XIST, SNHG16, DLEU1, CRNDE, SNHG6, DLGAP1, OSTM1-AS1, EMX2OS, H19). Analysis of the MDTE DB database revealed nephroblastoma-associated miRNAs that originate from retrotransposons. These include miR-192, -335, -378c, -562, -630, -1248. These molecules are promising for possible use in the pathogenetic treatment of Wilms’ tumor due to their effect on pathologically activated retrotransposons.

В обзорной статье приведены результаты анализа накопленных в литературе данных об ассоциации опухоли Вильмса с хромосомными синдромами и поиск возможных причин данного феномена. В 10 % всех случаев нефробластома представлена наследственным опухолевым синдромом вследствие герминальных мутаций в генах-супрессорах, главным образом в гене WT1, реже в WT2, WTX, CTNNB1, TP53. Данные гены характеризуются связью с ретроэлементами, которые играют важную роль в развитии опухоли Вильмса, способствуя канцерогенезу, вызывая геномную нестабильность. Ретроэлемент LINE-1 – негативный регулятор экспрессии WT1, в то время как гены-супрессоры подавляют активность ретроэлементов. Частью патогенеза синдромов Перлмана, Беквита–Видемана, WAGR, трисомии 18, обусловленных герминальными микроделециями, является активация ретроэлементов, способствующих соматическим хромосомным перестройкам, включая делеции, инсерции и транслокации, которые характерны для спорадической опухоли Вильмса. Кроме этого, ретроэлементы являются источниками длинных некодирующих РНК и микроРНК при процессинге их транскриптов или в эволюции генов. При этом длинные некодирующие РНК влияют на развитие опухоли Вильмса различными механизмами: за счет влияния на ферроптоз (lncRNA AC007406.1, AC005208.1, LINC01770, DLGAP1-AS2, AP002761.4, STPG3-AS1, AC129507.1, AC234772.2, LINC02447, AC009570.1, ZBTB20-AS1 и LINC01179), на сигнальные пути Wnt/β-катенина (HOTAIR, MEG3), апоптоз (HAGLROS), на регуляцию экспрессии специфических микроРНК (SNHG6, MEG8, XIST, SNHG16, DLEU1, CRNDE, SNHG6, DLGAP1, OSTM1-AS1, EMX2OS, H19).

Анализ базы данных MDTE DB позволил обнаружить ассоциированные с нефробластомой микроРНК, которые происходят от ретротранспозонов. К ним относятся miR-192, -335, -378c, -562, -630, -1248. Эти молекулы перспективны в отношении возможного использования для патогенетического лечения опухоли Вильмса вследствие воздействия на патологически активированные ретротранспозоны. 

 

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