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Synthetic lethal interactions of DEAD/H-box helicases as targets for cancer therapy

DEAD/H-box helicases are implicated in virtually every aspect of RNA metabolism, including transcription, pre-mRNA splicing, ribosomes biogenesis, nuclear export, translation initiation, RNA degradation, and mRNA editing. Most of these helicases are upregulated in various cancers and mutations in so...

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Autores principales: Arna, Ananna Bhadra, Patel, Hardikkumar, Singh, Ravi Shankar, Vizeacoumar, Frederick S., Kusalik, Anthony, Freywald, Andrew, Vizeacoumar, Franco J., Wu, Yuliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9905851/
https://www.ncbi.nlm.nih.gov/pubmed/36761420
http://dx.doi.org/10.3389/fonc.2022.1087989
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author Arna, Ananna Bhadra
Patel, Hardikkumar
Singh, Ravi Shankar
Vizeacoumar, Frederick S.
Kusalik, Anthony
Freywald, Andrew
Vizeacoumar, Franco J.
Wu, Yuliang
author_facet Arna, Ananna Bhadra
Patel, Hardikkumar
Singh, Ravi Shankar
Vizeacoumar, Frederick S.
Kusalik, Anthony
Freywald, Andrew
Vizeacoumar, Franco J.
Wu, Yuliang
author_sort Arna, Ananna Bhadra
collection PubMed
description DEAD/H-box helicases are implicated in virtually every aspect of RNA metabolism, including transcription, pre-mRNA splicing, ribosomes biogenesis, nuclear export, translation initiation, RNA degradation, and mRNA editing. Most of these helicases are upregulated in various cancers and mutations in some of them are associated with several malignancies. Lately, synthetic lethality (SL) and synthetic dosage lethality (SDL) approaches, where genetic interactions of cancer-related genes are exploited as therapeutic targets, are emerging as a leading area of cancer research. Several DEAD/H-box helicases, including DDX3, DDX9 (Dbp9), DDX10 (Dbp4), DDX11 (ChlR1), and DDX41 (Sacy-1), have been subjected to SL analyses in humans and different model organisms. It remains to be explored whether SDL can be utilized to identity druggable targets in DEAD/H-box helicase overexpressing cancers. In this review, we analyze gene expression data of a subset of DEAD/H-box helicases in multiple cancer types and discuss how their SL/SDL interactions can be used for therapeutic purposes. We also summarize the latest developments in clinical applications, apart from discussing some of the challenges in drug discovery in the context of targeting DEAD/H-box helicases.
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spelling pubmed-99058512023-02-08 Synthetic lethal interactions of DEAD/H-box helicases as targets for cancer therapy Arna, Ananna Bhadra Patel, Hardikkumar Singh, Ravi Shankar Vizeacoumar, Frederick S. Kusalik, Anthony Freywald, Andrew Vizeacoumar, Franco J. Wu, Yuliang Front Oncol Oncology DEAD/H-box helicases are implicated in virtually every aspect of RNA metabolism, including transcription, pre-mRNA splicing, ribosomes biogenesis, nuclear export, translation initiation, RNA degradation, and mRNA editing. Most of these helicases are upregulated in various cancers and mutations in some of them are associated with several malignancies. Lately, synthetic lethality (SL) and synthetic dosage lethality (SDL) approaches, where genetic interactions of cancer-related genes are exploited as therapeutic targets, are emerging as a leading area of cancer research. Several DEAD/H-box helicases, including DDX3, DDX9 (Dbp9), DDX10 (Dbp4), DDX11 (ChlR1), and DDX41 (Sacy-1), have been subjected to SL analyses in humans and different model organisms. It remains to be explored whether SDL can be utilized to identity druggable targets in DEAD/H-box helicase overexpressing cancers. In this review, we analyze gene expression data of a subset of DEAD/H-box helicases in multiple cancer types and discuss how their SL/SDL interactions can be used for therapeutic purposes. We also summarize the latest developments in clinical applications, apart from discussing some of the challenges in drug discovery in the context of targeting DEAD/H-box helicases. Frontiers Media S.A. 2023-01-26 /pmc/articles/PMC9905851/ /pubmed/36761420 http://dx.doi.org/10.3389/fonc.2022.1087989 Text en Copyright © 2023 Arna, Patel, Singh, Vizeacoumar, Kusalik, Freywald, Vizeacoumar and Wu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Arna, Ananna Bhadra
Patel, Hardikkumar
Singh, Ravi Shankar
Vizeacoumar, Frederick S.
Kusalik, Anthony
Freywald, Andrew
Vizeacoumar, Franco J.
Wu, Yuliang
Synthetic lethal interactions of DEAD/H-box helicases as targets for cancer therapy
title Synthetic lethal interactions of DEAD/H-box helicases as targets for cancer therapy
title_full Synthetic lethal interactions of DEAD/H-box helicases as targets for cancer therapy
title_fullStr Synthetic lethal interactions of DEAD/H-box helicases as targets for cancer therapy
title_full_unstemmed Synthetic lethal interactions of DEAD/H-box helicases as targets for cancer therapy
title_short Synthetic lethal interactions of DEAD/H-box helicases as targets for cancer therapy
title_sort synthetic lethal interactions of dead/h-box helicases as targets for cancer therapy
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9905851/
https://www.ncbi.nlm.nih.gov/pubmed/36761420
http://dx.doi.org/10.3389/fonc.2022.1087989
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