The probable role of retroelements in the development of Wilms’ tumor in chromosomal syndromes

Abstract

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.