Cargando…

Evaluating the Effect of 3′-UTR Variants in DICER1 and DROSHA on Their Tissue-Specific Expression by miRNA Target Prediction

Untranslated gene regions (UTRs) play an important role in controlling gene expression. 3′-UTRs are primarily targeted by microRNA (miRNA) molecules that form complex gene regulatory networks. Cancer genomes are replete with non-coding mutations, many of which are connected to changes in tumor gene...

Descripción completa

Detalles Bibliográficos
Autores principales: Bug, Dmitrii S., Tishkov, Artem V., Moiseev, Ivan S., Petukhova, Natalia V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8929110/
https://www.ncbi.nlm.nih.gov/pubmed/34287278
http://dx.doi.org/10.3390/cimb43020044
_version_ 1784670788143546368
author Bug, Dmitrii S.
Tishkov, Artem V.
Moiseev, Ivan S.
Petukhova, Natalia V.
author_facet Bug, Dmitrii S.
Tishkov, Artem V.
Moiseev, Ivan S.
Petukhova, Natalia V.
author_sort Bug, Dmitrii S.
collection PubMed
description Untranslated gene regions (UTRs) play an important role in controlling gene expression. 3′-UTRs are primarily targeted by microRNA (miRNA) molecules that form complex gene regulatory networks. Cancer genomes are replete with non-coding mutations, many of which are connected to changes in tumor gene expression that accompany the development of cancer and are associated with resistance to therapy. Therefore, variants that occurred in 3′-UTR under cancer progression should be analysed to predict their phenotypic effect on gene expression, e.g., by evaluating their impact on miRNA target sites. Here, we analyze 3′-UTR variants in DICER1 and DROSHA genes in the context of myelodysplastic syndrome (MDS) development. The key features of this analysis include an assessment of both “canonical” and “non-canonical” types of mRNA-miRNA binding and tissue-specific profiling of miRNA interactions with wild-type and mutated genes. As a result, we obtained a list of DICER1 and DROSHA variants likely altering the miRNA sites and, therefore, potentially leading to the observed tissue-specific gene downregulation. All identified variants have low population frequency consistent with their potential association with pathology progression.
format Online
Article
Text
id pubmed-8929110
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-89291102022-06-04 Evaluating the Effect of 3′-UTR Variants in DICER1 and DROSHA on Their Tissue-Specific Expression by miRNA Target Prediction Bug, Dmitrii S. Tishkov, Artem V. Moiseev, Ivan S. Petukhova, Natalia V. Curr Issues Mol Biol Article Untranslated gene regions (UTRs) play an important role in controlling gene expression. 3′-UTRs are primarily targeted by microRNA (miRNA) molecules that form complex gene regulatory networks. Cancer genomes are replete with non-coding mutations, many of which are connected to changes in tumor gene expression that accompany the development of cancer and are associated with resistance to therapy. Therefore, variants that occurred in 3′-UTR under cancer progression should be analysed to predict their phenotypic effect on gene expression, e.g., by evaluating their impact on miRNA target sites. Here, we analyze 3′-UTR variants in DICER1 and DROSHA genes in the context of myelodysplastic syndrome (MDS) development. The key features of this analysis include an assessment of both “canonical” and “non-canonical” types of mRNA-miRNA binding and tissue-specific profiling of miRNA interactions with wild-type and mutated genes. As a result, we obtained a list of DICER1 and DROSHA variants likely altering the miRNA sites and, therefore, potentially leading to the observed tissue-specific gene downregulation. All identified variants have low population frequency consistent with their potential association with pathology progression. MDPI 2021-07-06 /pmc/articles/PMC8929110/ /pubmed/34287278 http://dx.doi.org/10.3390/cimb43020044 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bug, Dmitrii S.
Tishkov, Artem V.
Moiseev, Ivan S.
Petukhova, Natalia V.
Evaluating the Effect of 3′-UTR Variants in DICER1 and DROSHA on Their Tissue-Specific Expression by miRNA Target Prediction
title Evaluating the Effect of 3′-UTR Variants in DICER1 and DROSHA on Their Tissue-Specific Expression by miRNA Target Prediction
title_full Evaluating the Effect of 3′-UTR Variants in DICER1 and DROSHA on Their Tissue-Specific Expression by miRNA Target Prediction
title_fullStr Evaluating the Effect of 3′-UTR Variants in DICER1 and DROSHA on Their Tissue-Specific Expression by miRNA Target Prediction
title_full_unstemmed Evaluating the Effect of 3′-UTR Variants in DICER1 and DROSHA on Their Tissue-Specific Expression by miRNA Target Prediction
title_short Evaluating the Effect of 3′-UTR Variants in DICER1 and DROSHA on Their Tissue-Specific Expression by miRNA Target Prediction
title_sort evaluating the effect of 3′-utr variants in dicer1 and drosha on their tissue-specific expression by mirna target prediction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8929110/
https://www.ncbi.nlm.nih.gov/pubmed/34287278
http://dx.doi.org/10.3390/cimb43020044
work_keys_str_mv AT bugdmitriis evaluatingtheeffectof3utrvariantsindicer1anddroshaontheirtissuespecificexpressionbymirnatargetprediction
AT tishkovartemv evaluatingtheeffectof3utrvariantsindicer1anddroshaontheirtissuespecificexpressionbymirnatargetprediction
AT moiseevivans evaluatingtheeffectof3utrvariantsindicer1anddroshaontheirtissuespecificexpressionbymirnatargetprediction
AT petukhovanataliav evaluatingtheeffectof3utrvariantsindicer1anddroshaontheirtissuespecificexpressionbymirnatargetprediction