Drugs targeting microRNAs that regulate DNA damage sensing and repair mechanisms: A computational drug discovery approach

Autores
Ravindranath, S. B.; Vratin, S.; Lakshmi, B. S.; Ramirez, Dario; Gomez Mejiba, Sandra Esther
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
DNA damage-sensing (DDS) and DNA damage-repair (DDR) mechanisms are essential for the fidelity of genetic information transmission. Failure to accomplish an effective DDS/DDR mechanism can lead to cell death or otherwise to cell transformation and cancer development. microRNAs (miRs) are short noncoding RNAs that primarily function as micromanagers of gene expression. Herein, we aimed to investigate the links between miRs and the translation of specific mRNAs encoding proteins involved in genomic DDS and DDR and to screen drugs that have high binding affinity to the selected miRs, which may serve as cancer therapeutics. To accomplish these aims, we used a variety of computational methods spanning data analysis, molecular modeling, and simulation tools (i.e., PyRx, Biopython, ViennaRNA, RNAComposer, AutoDock Vina, OpenBabel, PyMOL, Discovery Studio, MarvinSketch). The genes and miRNAs involved in the DDS and DDR mechanisms were retrieved from either the literature or various online databases (e.g., miRDB). miR data were further cleaned and prepared using scripts, and various libraries were used to obtain their 3-D structures. Genes interacting with miRs were enriched based on multiple database annotations using Enrichr KG. Then, we used docking analyses to virtually screen compounds to serve as ligands for the miRs. Finally, we generated gene-disease-miR-drug networks to study the linkages between the compounds and miR molecules under investigation. For the first time, we were able to identify five compounds that could be repurposed for downregulating miRs that are linked to inhibition of translation of mRNA involved in the DDS and DDR processes. The gathered candidate drugs can be useful for preventing cell transformation and cancer development.
Fil: Ravindranath, S. B.. Manipal Academy of Higher Education; India
Fil: Vratin, S.. University of Carnegie Mellon; Estados Unidos
Fil: Lakshmi, B. S.. Pes University; India
Fil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Gomez Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Materia
DNA DAMAGE
SENSING
GENE DISEASE
GENE EXPRESSION
MIR
COMPUTATIONAL DRUG DISCOVERY
MIR DRUG NETWORK
DNA DAMAGE REPAIR
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/266930
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/266930
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Drugs targeting microRNAs that regulate DNA damage sensing and repair mechanisms: A computational drug discovery approachRavindranath, S. B.Vratin, S.Lakshmi, B. S.Ramirez, DarioGomez Mejiba, Sandra EstherDNA DAMAGESENSINGGENE DISEASEGENE EXPRESSIONMIRCOMPUTATIONAL DRUG DISCOVERYMIR DRUG NETWORKDNA DAMAGE REPAIRhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1DNA damage-sensing (DDS) and DNA damage-repair (DDR) mechanisms are essential for the fidelity of genetic information transmission. Failure to accomplish an effective DDS/DDR mechanism can lead to cell death or otherwise to cell transformation and cancer development. microRNAs (miRs) are short noncoding RNAs that primarily function as micromanagers of gene expression. Herein, we aimed to investigate the links between miRs and the translation of specific mRNAs encoding proteins involved in genomic DDS and DDR and to screen drugs that have high binding affinity to the selected miRs, which may serve as cancer therapeutics. To accomplish these aims, we used a variety of computational methods spanning data analysis, molecular modeling, and simulation tools (i.e., PyRx, Biopython, ViennaRNA, RNAComposer, AutoDock Vina, OpenBabel, PyMOL, Discovery Studio, MarvinSketch). The genes and miRNAs involved in the DDS and DDR mechanisms were retrieved from either the literature or various online databases (e.g., miRDB). miR data were further cleaned and prepared using scripts, and various libraries were used to obtain their 3-D structures. Genes interacting with miRs were enriched based on multiple database annotations using Enrichr KG. Then, we used docking analyses to virtually screen compounds to serve as ligands for the miRs. Finally, we generated gene-disease-miR-drug networks to study the linkages between the compounds and miR molecules under investigation. For the first time, we were able to identify five compounds that could be repurposed for downregulating miRs that are linked to inhibition of translation of mRNA involved in the DDS and DDR processes. The gathered candidate drugs can be useful for preventing cell transformation and cancer development.Fil: Ravindranath, S. B.. Manipal Academy of Higher Education; IndiaFil: Vratin, S.. University of Carnegie Mellon; Estados UnidosFil: Lakshmi, B. S.. Pes University; IndiaFil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Gomez Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaCold Spring Harbor Laboratory Press2024-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/266930Ravindranath, S. B.; Vratin, S.; Lakshmi, B. S.; Ramirez, Dario; Gomez Mejiba, Sandra Esther; Drugs targeting microRNAs that regulate DNA damage sensing and repair mechanisms: A computational drug discovery approach; Cold Spring Harbor Laboratory Press; BioRxiv; 6-2024; 1-442692-82052692-8205CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1101/2024.06.18.599590info:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2024.06.18.599590v1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:42:21Zoai:ri.conicet.gov.ar:11336/266930instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:42:21.849CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Drugs targeting microRNAs that regulate DNA damage sensing and repair mechanisms: A computational drug discovery approach
title Drugs targeting microRNAs that regulate DNA damage sensing and repair mechanisms: A computational drug discovery approach
spellingShingle Drugs targeting microRNAs that regulate DNA damage sensing and repair mechanisms: A computational drug discovery approach
Ravindranath, S. B.
DNA DAMAGE
SENSING
GENE DISEASE
GENE EXPRESSION
MIR
COMPUTATIONAL DRUG DISCOVERY
MIR DRUG NETWORK
DNA DAMAGE REPAIR
title_short Drugs targeting microRNAs that regulate DNA damage sensing and repair mechanisms: A computational drug discovery approach
title_full Drugs targeting microRNAs that regulate DNA damage sensing and repair mechanisms: A computational drug discovery approach
title_fullStr Drugs targeting microRNAs that regulate DNA damage sensing and repair mechanisms: A computational drug discovery approach
title_full_unstemmed Drugs targeting microRNAs that regulate DNA damage sensing and repair mechanisms: A computational drug discovery approach
title_sort Drugs targeting microRNAs that regulate DNA damage sensing and repair mechanisms: A computational drug discovery approach
dc.creator.none.fl_str_mv Ravindranath, S. B.
Vratin, S.
Lakshmi, B. S.
Ramirez, Dario
Gomez Mejiba, Sandra Esther
author Ravindranath, S. B.
author_facet Ravindranath, S. B.
Vratin, S.
Lakshmi, B. S.
Ramirez, Dario
Gomez Mejiba, Sandra Esther
author_role author
author2 Vratin, S.
Lakshmi, B. S.
Ramirez, Dario
Gomez Mejiba, Sandra Esther
author2_role author
author
author
author
dc.subject.none.fl_str_mv DNA DAMAGE
SENSING
GENE DISEASE
GENE EXPRESSION
MIR
COMPUTATIONAL DRUG DISCOVERY
MIR DRUG NETWORK
DNA DAMAGE REPAIR
topic DNA DAMAGE
SENSING
GENE DISEASE
GENE EXPRESSION
MIR
COMPUTATIONAL DRUG DISCOVERY
MIR DRUG NETWORK
DNA DAMAGE REPAIR
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv DNA damage-sensing (DDS) and DNA damage-repair (DDR) mechanisms are essential for the fidelity of genetic information transmission. Failure to accomplish an effective DDS/DDR mechanism can lead to cell death or otherwise to cell transformation and cancer development. microRNAs (miRs) are short noncoding RNAs that primarily function as micromanagers of gene expression. Herein, we aimed to investigate the links between miRs and the translation of specific mRNAs encoding proteins involved in genomic DDS and DDR and to screen drugs that have high binding affinity to the selected miRs, which may serve as cancer therapeutics. To accomplish these aims, we used a variety of computational methods spanning data analysis, molecular modeling, and simulation tools (i.e., PyRx, Biopython, ViennaRNA, RNAComposer, AutoDock Vina, OpenBabel, PyMOL, Discovery Studio, MarvinSketch). The genes and miRNAs involved in the DDS and DDR mechanisms were retrieved from either the literature or various online databases (e.g., miRDB). miR data were further cleaned and prepared using scripts, and various libraries were used to obtain their 3-D structures. Genes interacting with miRs were enriched based on multiple database annotations using Enrichr KG. Then, we used docking analyses to virtually screen compounds to serve as ligands for the miRs. Finally, we generated gene-disease-miR-drug networks to study the linkages between the compounds and miR molecules under investigation. For the first time, we were able to identify five compounds that could be repurposed for downregulating miRs that are linked to inhibition of translation of mRNA involved in the DDS and DDR processes. The gathered candidate drugs can be useful for preventing cell transformation and cancer development.
Fil: Ravindranath, S. B.. Manipal Academy of Higher Education; India
Fil: Vratin, S.. University of Carnegie Mellon; Estados Unidos
Fil: Lakshmi, B. S.. Pes University; India
Fil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Gomez Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
description DNA damage-sensing (DDS) and DNA damage-repair (DDR) mechanisms are essential for the fidelity of genetic information transmission. Failure to accomplish an effective DDS/DDR mechanism can lead to cell death or otherwise to cell transformation and cancer development. microRNAs (miRs) are short noncoding RNAs that primarily function as micromanagers of gene expression. Herein, we aimed to investigate the links between miRs and the translation of specific mRNAs encoding proteins involved in genomic DDS and DDR and to screen drugs that have high binding affinity to the selected miRs, which may serve as cancer therapeutics. To accomplish these aims, we used a variety of computational methods spanning data analysis, molecular modeling, and simulation tools (i.e., PyRx, Biopython, ViennaRNA, RNAComposer, AutoDock Vina, OpenBabel, PyMOL, Discovery Studio, MarvinSketch). The genes and miRNAs involved in the DDS and DDR mechanisms were retrieved from either the literature or various online databases (e.g., miRDB). miR data were further cleaned and prepared using scripts, and various libraries were used to obtain their 3-D structures. Genes interacting with miRs were enriched based on multiple database annotations using Enrichr KG. Then, we used docking analyses to virtually screen compounds to serve as ligands for the miRs. Finally, we generated gene-disease-miR-drug networks to study the linkages between the compounds and miR molecules under investigation. For the first time, we were able to identify five compounds that could be repurposed for downregulating miRs that are linked to inhibition of translation of mRNA involved in the DDS and DDR processes. The gathered candidate drugs can be useful for preventing cell transformation and cancer development.
publishDate 2024
dc.date.none.fl_str_mv 2024-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/266930
Ravindranath, S. B.; Vratin, S.; Lakshmi, B. S.; Ramirez, Dario; Gomez Mejiba, Sandra Esther; Drugs targeting microRNAs that regulate DNA damage sensing and repair mechanisms: A computational drug discovery approach; Cold Spring Harbor Laboratory Press; BioRxiv; 6-2024; 1-44
2692-8205
2692-8205
CONICET Digital
CONICET
url http://hdl.handle.net/11336/266930
identifier_str_mv Ravindranath, S. B.; Vratin, S.; Lakshmi, B. S.; Ramirez, Dario; Gomez Mejiba, Sandra Esther; Drugs targeting microRNAs that regulate DNA damage sensing and repair mechanisms: A computational drug discovery approach; Cold Spring Harbor Laboratory Press; BioRxiv; 6-2024; 1-44
2692-8205
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1101/2024.06.18.599590
info:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2024.06.18.599590v1
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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