miR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD Approach

Detalhes bibliográficos
Autor(a) principal: Santos, Sergio Alexandre Alcantara [UNESP]
Data de Publicação: 2022
Outros Autores: Portela, Luiz Marcos Frediani [UNESP], Camargo, Ana Carolina Lima [UNESP], Constantino, Flavia Bessi [UNESP], Colombelli, Ketlin Thassiani [UNESP], Fioretto, Matheus Naia [UNESP], Mattos, Renato [UNESP], de Almeida Fantinatti, Bruno Evaristo [UNESP], Denti, Michela Alessandra, Piazza, Silvano, Felisbino, Sérgio Luis [UNESP], Zambrano, Elena, Justulin, Luis Antonio [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.3390/ijms232314855
http://hdl.handle.net/11449/249463
Resumo: The Developmental Origins of Health and Disease (DOHaD) concept correlates early life exposure to stressor conditions with the increased incidence of non-communicable chronic diseases, including prostate cancer (PCa), throughout the life span. However, the molecular mechanisms involved in this process remain poorly understood. In this study, the deregulation of two miRNAs (rno-miR-18a-5p and rno-miR-345-3p) was described in the ventral prostate VP of old rats born to dams fed with a low protein diet (LPD) (6% protein in the diet) during gestational and lactational periods. Integrative analysis of the (VP) transcriptomic and proteomic data revealed changes in the expression profile of 14 identified predicted targets of these two DE miRNAs, which enriched terms related to post-translational protein modification, metabolism of proteins, protein processing in endoplasmic reticulum, phosphonate and phosphinate metabolism, the calnexin/calreticulin cycle, metabolic pathways, N-glycan trimming in the ER and the calnexin/calreticulin cycle, hedgehog ligand biogenesis, the ER-phagosome pathway, detoxification of reactive oxygen species, antigenprocessing-cross presentation, RAB geranylgeranylation, collagen formation, glutathione metabolism, the metabolism of xenobiotics by cytochrome P450, and platinum drug resistance. RT-qPCR validated the deregulation of the miR-18a-5p/P4HB (prolyl 4-hydroxylase subunit beta) network in the VP of older offspring as well as in the PNT-2 cells transfected with mimic miR-18a-5p. Functional in vitro studies revealed a potential modulation of estrogen receptor α (ESR1) by miR-18a-5p in PNT-2 cells, which was also confirmed in the VP of older offspring. An imbalance of the testosterone/estrogen ratio was also observed in the offspring rats born to dams fed with an LPD. In conclusion, deregulation of the miR-18a-5p/P4HB network can contribute to the developmental origins of prostate cancer in maternally malnourished offspring, highlighting the need for improving maternal healthcare during critical windows of vulnerability early in life.
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spelling miR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD ApproachagingDevelopmental Origins of Health and Disease (DOHaD)epigeneticsmiR-18a-5p/P4HB networkprostate cancerThe Developmental Origins of Health and Disease (DOHaD) concept correlates early life exposure to stressor conditions with the increased incidence of non-communicable chronic diseases, including prostate cancer (PCa), throughout the life span. However, the molecular mechanisms involved in this process remain poorly understood. In this study, the deregulation of two miRNAs (rno-miR-18a-5p and rno-miR-345-3p) was described in the ventral prostate VP of old rats born to dams fed with a low protein diet (LPD) (6% protein in the diet) during gestational and lactational periods. Integrative analysis of the (VP) transcriptomic and proteomic data revealed changes in the expression profile of 14 identified predicted targets of these two DE miRNAs, which enriched terms related to post-translational protein modification, metabolism of proteins, protein processing in endoplasmic reticulum, phosphonate and phosphinate metabolism, the calnexin/calreticulin cycle, metabolic pathways, N-glycan trimming in the ER and the calnexin/calreticulin cycle, hedgehog ligand biogenesis, the ER-phagosome pathway, detoxification of reactive oxygen species, antigenprocessing-cross presentation, RAB geranylgeranylation, collagen formation, glutathione metabolism, the metabolism of xenobiotics by cytochrome P450, and platinum drug resistance. RT-qPCR validated the deregulation of the miR-18a-5p/P4HB (prolyl 4-hydroxylase subunit beta) network in the VP of older offspring as well as in the PNT-2 cells transfected with mimic miR-18a-5p. Functional in vitro studies revealed a potential modulation of estrogen receptor α (ESR1) by miR-18a-5p in PNT-2 cells, which was also confirmed in the VP of older offspring. An imbalance of the testosterone/estrogen ratio was also observed in the offspring rats born to dams fed with an LPD. In conclusion, deregulation of the miR-18a-5p/P4HB network can contribute to the developmental origins of prostate cancer in maternally malnourished offspring, highlighting the need for improving maternal healthcare during critical windows of vulnerability early in life.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Structural and Functional Biology Institute of Biosciences Sao Paulo State University (UNESP) Unesp Botucatu, SPCancer Signaling and Epigenetics Program Fox Chase Cancer CenterDepartment of Cellular Computational and Integrative Biology—CIBIO University of TrentoDepartamento de Biología de la Reproducción Instituto Nacional de Ciencias Médicas y Nutrición, Salvador ZubiránDepartment of Structural and Functional Biology Institute of Biosciences Sao Paulo State University (UNESP) Unesp Botucatu, SPCNPq: 310663/2018-0Universidade Estadual Paulista (UNESP)Fox Chase Cancer CenterUniversity of TrentoInstituto Nacional de Ciencias Médicas y NutriciónSantos, Sergio Alexandre Alcantara [UNESP]Portela, Luiz Marcos Frediani [UNESP]Camargo, Ana Carolina Lima [UNESP]Constantino, Flavia Bessi [UNESP]Colombelli, Ketlin Thassiani [UNESP]Fioretto, Matheus Naia [UNESP]Mattos, Renato [UNESP]de Almeida Fantinatti, Bruno Evaristo [UNESP]Denti, Michela AlessandraPiazza, SilvanoFelisbino, Sérgio Luis [UNESP]Zambrano, ElenaJustulin, Luis Antonio [UNESP]2023-07-29T15:41:59Z2023-07-29T15:41:59Z2022-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/ijms232314855International Journal of Molecular Sciences, v. 23, n. 23, 2022.1422-00671661-6596http://hdl.handle.net/11449/24946310.3390/ijms2323148552-s2.0-85143775663Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Molecular Sciencesinfo:eu-repo/semantics/openAccess2023-07-29T15:41:59Zoai:repositorio.unesp.br:11449/249463Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:22:31.606706Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv miR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD Approach
title miR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD Approach
spellingShingle miR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD Approach
Santos, Sergio Alexandre Alcantara [UNESP]
aging
Developmental Origins of Health and Disease (DOHaD)
epigenetics
miR-18a-5p/P4HB network
prostate cancer
title_short miR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD Approach
title_full miR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD Approach
title_fullStr miR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD Approach
title_full_unstemmed miR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD Approach
title_sort miR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD Approach
author Santos, Sergio Alexandre Alcantara [UNESP]
author_facet Santos, Sergio Alexandre Alcantara [UNESP]
Portela, Luiz Marcos Frediani [UNESP]
Camargo, Ana Carolina Lima [UNESP]
Constantino, Flavia Bessi [UNESP]
Colombelli, Ketlin Thassiani [UNESP]
Fioretto, Matheus Naia [UNESP]
Mattos, Renato [UNESP]
de Almeida Fantinatti, Bruno Evaristo [UNESP]
Denti, Michela Alessandra
Piazza, Silvano
Felisbino, Sérgio Luis [UNESP]
Zambrano, Elena
Justulin, Luis Antonio [UNESP]
author_role author
author2 Portela, Luiz Marcos Frediani [UNESP]
Camargo, Ana Carolina Lima [UNESP]
Constantino, Flavia Bessi [UNESP]
Colombelli, Ketlin Thassiani [UNESP]
Fioretto, Matheus Naia [UNESP]
Mattos, Renato [UNESP]
de Almeida Fantinatti, Bruno Evaristo [UNESP]
Denti, Michela Alessandra
Piazza, Silvano
Felisbino, Sérgio Luis [UNESP]
Zambrano, Elena
Justulin, Luis Antonio [UNESP]
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (UNESP)
Fox Chase Cancer Center
University of Trento
Instituto Nacional de Ciencias Médicas y Nutrición
dc.contributor.author.fl_str_mv Santos, Sergio Alexandre Alcantara [UNESP]
Portela, Luiz Marcos Frediani [UNESP]
Camargo, Ana Carolina Lima [UNESP]
Constantino, Flavia Bessi [UNESP]
Colombelli, Ketlin Thassiani [UNESP]
Fioretto, Matheus Naia [UNESP]
Mattos, Renato [UNESP]
de Almeida Fantinatti, Bruno Evaristo [UNESP]
Denti, Michela Alessandra
Piazza, Silvano
Felisbino, Sérgio Luis [UNESP]
Zambrano, Elena
Justulin, Luis Antonio [UNESP]
dc.subject.por.fl_str_mv aging
Developmental Origins of Health and Disease (DOHaD)
epigenetics
miR-18a-5p/P4HB network
prostate cancer
topic aging
Developmental Origins of Health and Disease (DOHaD)
epigenetics
miR-18a-5p/P4HB network
prostate cancer
description The Developmental Origins of Health and Disease (DOHaD) concept correlates early life exposure to stressor conditions with the increased incidence of non-communicable chronic diseases, including prostate cancer (PCa), throughout the life span. However, the molecular mechanisms involved in this process remain poorly understood. In this study, the deregulation of two miRNAs (rno-miR-18a-5p and rno-miR-345-3p) was described in the ventral prostate VP of old rats born to dams fed with a low protein diet (LPD) (6% protein in the diet) during gestational and lactational periods. Integrative analysis of the (VP) transcriptomic and proteomic data revealed changes in the expression profile of 14 identified predicted targets of these two DE miRNAs, which enriched terms related to post-translational protein modification, metabolism of proteins, protein processing in endoplasmic reticulum, phosphonate and phosphinate metabolism, the calnexin/calreticulin cycle, metabolic pathways, N-glycan trimming in the ER and the calnexin/calreticulin cycle, hedgehog ligand biogenesis, the ER-phagosome pathway, detoxification of reactive oxygen species, antigenprocessing-cross presentation, RAB geranylgeranylation, collagen formation, glutathione metabolism, the metabolism of xenobiotics by cytochrome P450, and platinum drug resistance. RT-qPCR validated the deregulation of the miR-18a-5p/P4HB (prolyl 4-hydroxylase subunit beta) network in the VP of older offspring as well as in the PNT-2 cells transfected with mimic miR-18a-5p. Functional in vitro studies revealed a potential modulation of estrogen receptor α (ESR1) by miR-18a-5p in PNT-2 cells, which was also confirmed in the VP of older offspring. An imbalance of the testosterone/estrogen ratio was also observed in the offspring rats born to dams fed with an LPD. In conclusion, deregulation of the miR-18a-5p/P4HB network can contribute to the developmental origins of prostate cancer in maternally malnourished offspring, highlighting the need for improving maternal healthcare during critical windows of vulnerability early in life.
publishDate 2022
dc.date.none.fl_str_mv 2022-12-01
2023-07-29T15:41:59Z
2023-07-29T15:41:59Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.3390/ijms232314855
International Journal of Molecular Sciences, v. 23, n. 23, 2022.
1422-0067
1661-6596
http://hdl.handle.net/11449/249463
10.3390/ijms232314855
2-s2.0-85143775663
url http://dx.doi.org/10.3390/ijms232314855
http://hdl.handle.net/11449/249463
identifier_str_mv International Journal of Molecular Sciences, v. 23, n. 23, 2022.
1422-0067
1661-6596
10.3390/ijms232314855
2-s2.0-85143775663
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv International Journal of Molecular Sciences
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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