Identification and molecular characterization of bone-related micrornas: functional implications

Detalhes bibliográficos
Autor(a) principal: Roberto, Vania Palma
Data de Publicação: 2014
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.1/7080
Resumo: MicroRNAs (miRNAs) are a conserved class of small RNAs providing a post-transcriptional mechanism for fine-tuning of intricate physiological and pathological cellular processes, such as those affecting development. Skeletogenesis however, was so far poorly investigated and mainly focused on mammalian models, with a general lack of knowledge concerning other vertebrates. We aimed at the identification of bone-related miRNAs and their characterization from an evolutionary perspective, using fish (mostly zebrafish) as model, in comparison to mammalian systems. First, we focused on miR-223, a miRNA that was associated with bone remodelling. We demonstrated that miR-223 genomic organization/context and primary/secondary structures are largely maintained between human and zebrafish. As in mammals, miR-223 expression in zebrafish was highly correlated with hematopoietic events and osteoclastogenesis. Finally, miR-223 targets identified in mammals were also predicted in zebrafish, supporting a functional conservation of this miRNA. In a second set of experiments, we studied the biological role of miR-29a, a bone-related miRNA that was fairly investigated in mammals, but with no mineralogenic effects yet demonstrated. We took advantage of our fish bone-derived systems to explore miR-29a mineralogenic effects through gain-of-function experiments. We demonstrated a strong stimulation of this process through a mechanism probably involving the canonical Wnt signalling. Once more, through bioinformatics analysis, patterns of expression and target prediction/validation, we provided evidences for miR-29 conservation throughout evolution. Finally, we explored miR-214 putative roles on skeleton formation in vertebrates. Although our initial hypothesis of miR-214 involvement in osteogenesis was recently demonstrated by Wang et al. (2013), we proceeded with our investigation and finally showed that miR-214 is also associated with chondrogenesis. Overexpression of miR-214 in ATDC5 cells mitigated differentiation and down-regulated Mgp and Osteocalcin, probably by targeting Atf4. This work provides novel evidence that some miRNAs have conserved functions across vertebrates and, probably, conserved regulatory mechanisms of action.
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spelling Identification and molecular characterization of bone-related micrornas: functional implicationsCiências biomédicasConservaçãoPeixe-zebraOssosManipulação genéticaMicroRNAs (miRNAs) are a conserved class of small RNAs providing a post-transcriptional mechanism for fine-tuning of intricate physiological and pathological cellular processes, such as those affecting development. Skeletogenesis however, was so far poorly investigated and mainly focused on mammalian models, with a general lack of knowledge concerning other vertebrates. We aimed at the identification of bone-related miRNAs and their characterization from an evolutionary perspective, using fish (mostly zebrafish) as model, in comparison to mammalian systems. First, we focused on miR-223, a miRNA that was associated with bone remodelling. We demonstrated that miR-223 genomic organization/context and primary/secondary structures are largely maintained between human and zebrafish. As in mammals, miR-223 expression in zebrafish was highly correlated with hematopoietic events and osteoclastogenesis. Finally, miR-223 targets identified in mammals were also predicted in zebrafish, supporting a functional conservation of this miRNA. In a second set of experiments, we studied the biological role of miR-29a, a bone-related miRNA that was fairly investigated in mammals, but with no mineralogenic effects yet demonstrated. We took advantage of our fish bone-derived systems to explore miR-29a mineralogenic effects through gain-of-function experiments. We demonstrated a strong stimulation of this process through a mechanism probably involving the canonical Wnt signalling. Once more, through bioinformatics analysis, patterns of expression and target prediction/validation, we provided evidences for miR-29 conservation throughout evolution. Finally, we explored miR-214 putative roles on skeleton formation in vertebrates. Although our initial hypothesis of miR-214 involvement in osteogenesis was recently demonstrated by Wang et al. (2013), we proceeded with our investigation and finally showed that miR-214 is also associated with chondrogenesis. Overexpression of miR-214 in ATDC5 cells mitigated differentiation and down-regulated Mgp and Osteocalcin, probably by targeting Atf4. This work provides novel evidence that some miRNAs have conserved functions across vertebrates and, probably, conserved regulatory mechanisms of action.Cancela, LeonorTiago, DanielGautvik, KaareSapientiaRoberto, Vania Palma2017-12-10T01:30:10Z201420142014-01-01T00:00:00Zdoctoral thesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10400.1/7080enginfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-11-29T10:39:06Zoai:sapientia.ualg.pt:10400.1/7080Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-11-29T10:39:06Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Identification and molecular characterization of bone-related micrornas: functional implications
title Identification and molecular characterization of bone-related micrornas: functional implications
spellingShingle Identification and molecular characterization of bone-related micrornas: functional implications
Roberto, Vania Palma
Ciências biomédicas
Conservação
Peixe-zebra
Ossos
Manipulação genética
title_short Identification and molecular characterization of bone-related micrornas: functional implications
title_full Identification and molecular characterization of bone-related micrornas: functional implications
title_fullStr Identification and molecular characterization of bone-related micrornas: functional implications
title_full_unstemmed Identification and molecular characterization of bone-related micrornas: functional implications
title_sort Identification and molecular characterization of bone-related micrornas: functional implications
author Roberto, Vania Palma
author_facet Roberto, Vania Palma
author_role author
dc.contributor.none.fl_str_mv Cancela, Leonor
Tiago, Daniel
Gautvik, Kaare
Sapientia
dc.contributor.author.fl_str_mv Roberto, Vania Palma
dc.subject.por.fl_str_mv Ciências biomédicas
Conservação
Peixe-zebra
Ossos
Manipulação genética
topic Ciências biomédicas
Conservação
Peixe-zebra
Ossos
Manipulação genética
description MicroRNAs (miRNAs) are a conserved class of small RNAs providing a post-transcriptional mechanism for fine-tuning of intricate physiological and pathological cellular processes, such as those affecting development. Skeletogenesis however, was so far poorly investigated and mainly focused on mammalian models, with a general lack of knowledge concerning other vertebrates. We aimed at the identification of bone-related miRNAs and their characterization from an evolutionary perspective, using fish (mostly zebrafish) as model, in comparison to mammalian systems. First, we focused on miR-223, a miRNA that was associated with bone remodelling. We demonstrated that miR-223 genomic organization/context and primary/secondary structures are largely maintained between human and zebrafish. As in mammals, miR-223 expression in zebrafish was highly correlated with hematopoietic events and osteoclastogenesis. Finally, miR-223 targets identified in mammals were also predicted in zebrafish, supporting a functional conservation of this miRNA. In a second set of experiments, we studied the biological role of miR-29a, a bone-related miRNA that was fairly investigated in mammals, but with no mineralogenic effects yet demonstrated. We took advantage of our fish bone-derived systems to explore miR-29a mineralogenic effects through gain-of-function experiments. We demonstrated a strong stimulation of this process through a mechanism probably involving the canonical Wnt signalling. Once more, through bioinformatics analysis, patterns of expression and target prediction/validation, we provided evidences for miR-29 conservation throughout evolution. Finally, we explored miR-214 putative roles on skeleton formation in vertebrates. Although our initial hypothesis of miR-214 involvement in osteogenesis was recently demonstrated by Wang et al. (2013), we proceeded with our investigation and finally showed that miR-214 is also associated with chondrogenesis. Overexpression of miR-214 in ATDC5 cells mitigated differentiation and down-regulated Mgp and Osteocalcin, probably by targeting Atf4. This work provides novel evidence that some miRNAs have conserved functions across vertebrates and, probably, conserved regulatory mechanisms of action.
publishDate 2014
dc.date.none.fl_str_mv 2014
2014
2014-01-01T00:00:00Z
2017-12-10T01:30:10Z
dc.type.driver.fl_str_mv doctoral thesis
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.1/7080
url http://hdl.handle.net/10400.1/7080
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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