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The role of miRNA biogenesis and DDX17 in tumorigenesis and cancer stemness

Cancer stemness represents one of the major mechanisms that predispose patients to tumor aggressiveness, metastasis, and treatment resistance. MicroRNA biogenesis is an important process controlling miRNA processing and maturation. Deregulation of miRNA biogenesis can lead to tumorigenesis and cance...

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Autor principal: Wu, Kou-Juey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Chang Gung University 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283569/
https://www.ncbi.nlm.nih.gov/pubmed/32513392
http://dx.doi.org/10.1016/j.bj.2020.03.001
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author Wu, Kou-Juey
author_facet Wu, Kou-Juey
author_sort Wu, Kou-Juey
collection PubMed
description Cancer stemness represents one of the major mechanisms that predispose patients to tumor aggressiveness, metastasis, and treatment resistance. MicroRNA biogenesis is an important process controlling miRNA processing and maturation. Deregulation of miRNA biogenesis can lead to tumorigenesis and cancer stemness. DDX17 is a co-factor of the miRNA microprocessor. Misregulation of DDX17 can be associated with cancer stemness. K63-linked polyubiquitination of DDX17 presents a concerted mechanism of decreased synthesis of stemness-inhibiting miRNAs and increased transcriptional activation of stemness-related gene expression. K63-linked polyubiquitination of HAUSP serves as a scaffold to anchor HIF-1α, CBP, the mediator complex, and the super-elongation complex to enhance HIF-1α-induced gene transcription. Recent progress in RNA modifications shows that RNA N6-methyladenosine (m6A) modification is a crucial mechanism to regulate RNA levels. M6A modification of miRNAs can also be linked to tumorigenesis and cancer stemness. Overall, miRNA biogenesis and K63-linked polyubiquitination of DDX17 play an important role in the induction of cancer stemness. Delineation of the mechanisms and identification of suitable targets may provide new therapeutic options for treatment-resistant cancers.
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spelling pubmed-72835692020-06-15 The role of miRNA biogenesis and DDX17 in tumorigenesis and cancer stemness Wu, Kou-Juey Biomed J Review Article Cancer stemness represents one of the major mechanisms that predispose patients to tumor aggressiveness, metastasis, and treatment resistance. MicroRNA biogenesis is an important process controlling miRNA processing and maturation. Deregulation of miRNA biogenesis can lead to tumorigenesis and cancer stemness. DDX17 is a co-factor of the miRNA microprocessor. Misregulation of DDX17 can be associated with cancer stemness. K63-linked polyubiquitination of DDX17 presents a concerted mechanism of decreased synthesis of stemness-inhibiting miRNAs and increased transcriptional activation of stemness-related gene expression. K63-linked polyubiquitination of HAUSP serves as a scaffold to anchor HIF-1α, CBP, the mediator complex, and the super-elongation complex to enhance HIF-1α-induced gene transcription. Recent progress in RNA modifications shows that RNA N6-methyladenosine (m6A) modification is a crucial mechanism to regulate RNA levels. M6A modification of miRNAs can also be linked to tumorigenesis and cancer stemness. Overall, miRNA biogenesis and K63-linked polyubiquitination of DDX17 play an important role in the induction of cancer stemness. Delineation of the mechanisms and identification of suitable targets may provide new therapeutic options for treatment-resistant cancers. Chang Gung University 2020-04 2020-04-13 /pmc/articles/PMC7283569/ /pubmed/32513392 http://dx.doi.org/10.1016/j.bj.2020.03.001 Text en © 2020 Chang Gung University. Publishing services by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review Article
Wu, Kou-Juey
The role of miRNA biogenesis and DDX17 in tumorigenesis and cancer stemness
title The role of miRNA biogenesis and DDX17 in tumorigenesis and cancer stemness
title_full The role of miRNA biogenesis and DDX17 in tumorigenesis and cancer stemness
title_fullStr The role of miRNA biogenesis and DDX17 in tumorigenesis and cancer stemness
title_full_unstemmed The role of miRNA biogenesis and DDX17 in tumorigenesis and cancer stemness
title_short The role of miRNA biogenesis and DDX17 in tumorigenesis and cancer stemness
title_sort role of mirna biogenesis and ddx17 in tumorigenesis and cancer stemness
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283569/
https://www.ncbi.nlm.nih.gov/pubmed/32513392
http://dx.doi.org/10.1016/j.bj.2020.03.001
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