miR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD Approach
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , |
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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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 |
|
_version_ |
1808129314330247168 |