Frequency, spectrum, and functional significance of mutations in the MIR-142 gene in diffuse large B-cell cell lymphoma
Background:MIR-142 is the only human microRNA gene that is highly mutated in diffuse large B-cell lymphoma (DLBCL). Early studies of abnormalities in this gene were based on the analysis of several lymphoma biospecimens and did not focus on assessing the functional effect of the detected changes. The aim of the study:To describe the frequency and spectrum of mutations in the MIR-142 gene in a large sample of tumor tissue samples from patients with DLBCL, as well as to analyze their functional significance in silico. Materials and methods: Direct Sanger sequencing of the MIR-142 gene was performed in 123 DNA samples isolated from sections of FFPE blocks from biopsies of tumor lymph nodes in patients with DLBCL. In silico prediction of target genes for each of the "seed" microRNA sequences was performed using the miRDB online tool. To determine the function of microRNA target genes, an analysis of the enrichment of terms of gene ontologies of molecular functions and biological processes using PANTHER based on the bioinformatics resource Gene Ontology was carried out. To predict the secondary structure of the microRNA hairpin and calculate its minimum free energy (dG), we used UNAfold web server. Results: The mutation rate in the study group was 16.7%, and in three cases there were multiple single-nucleotide substitutions in the MIR-142 sequence. A total of 24 types of single nucleotide substitutions were identified, with transitions prevailing over transversions. An analysis of the distribution of mutations in the sequence of the MIR-142 gene showed that only 15% were localized in "key" regions, while the majority were located outside it: in the sequence of mature strands (30%), the precursor (40%) or the primary transcript (10%) of microRNAs. An in silico analysis of the effect of substitutions located in the "seed" sequence on microRNA-mRNA interactions showed that all three mutations identified in the study group lead to a significant change in the set of regulated genes. The most pronounced changes in the spectrum of regulated genes were found for n.68G/A. Almost all of the mutations we described affected the structure and thermal stability of the hairpin microRNAs to one degree or another. Conclusion: The data obtained indicate a significant effect of mutations in the "seed" sequence on the switching of target genes in the mature strands of the microRNA under study. Further functional studies needed to confirm the effect of the predicted changes in thermodynamic stability and secondary structure on the biogenesis of mature microRNA strands
Voropaeva EN, Seregina OB, Voytko MS, et al. Frequency, spectrum, and functional
significance of mutations in the MIR-142 gene in diffuse large B-cell cell lymphoma. Research
Results in Biomedicine. 2025;11(4):607-627. Russian. DOI: 10.18413/2658-6533-2025-11-4-0-2
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