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MiR-146b negatively regulates migration and delays progression of T-cell acute lymphoblastic leukemia

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dc.contributor.authorCorreia, Nádia
dc.contributor.authorFragoso, Rita
dc.contributor.authorCarvalho, Tânia
dc.contributor.authorEnguita, Francisco J.
dc.contributor.authorBarata, João T.
dc.date.accessioned2021-10-14T11:12:48Z
dc.date.available2021-10-14T11:12:48Z
dc.date.issued2016
dc.description© The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/pt_PT
dc.description.abstractPrevious results indicated that miR-146b-5p is downregulated by TAL1, a transcription factor critical for early hematopoiesis that is frequently overexpressed in T-cell acute lymphoblastic leukemia (T-ALL) where it has an oncogenic role. Here, we confirmed that miR-146b-5p expression is lower in TAL1-positive patient samples than in other T-ALL cases. Furthermore, leukemia T-cells display decreased levels of miR-146b-5p as compared to normal T-cells, thymocytes and other hematopoietic progenitors. MiR-146b-5p silencing enhances the in vitro migration and invasion of T-ALL cells, associated with increased levels of filamentous actin and chemokinesis. In vivo, miR-146b overexpression in a TAL1-positive cell line extends mouse survival in a xenotransplant model of human T-ALL. In contrast, knockdown of miR-146b-5p results in leukemia acceleration and decreased mouse overall survival, paralleled by faster tumor infiltration of the central nervous system. Our results suggest that miR-146b-5p is a functionally relevant microRNA gene in the context of T-ALL, whose negative regulation by TAL1 and possibly other oncogenes contributes to disease progression by modulating leukemia cell motility and disease aggressiveness.pt_PT
dc.description.sponsorshipThese studies were supported by Liga Portuguesa Contra o Cancro (Terry Fox Award) and by Fundação para a Ciência e a Tecnologia (project PTDC/BIM-ONC/1548/2012). N.C.C. received an FCT-SFRH PhD fellowship. R.F. and J.T.B. are supported by FCT investigator Starting and Consolidation grants, respectively.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationSci Rep. 2016 Aug 23;6:31894pt_PT
dc.identifier.doi10.1038/srep31894pt_PT
dc.identifier.eissn2045-2322
dc.identifier.urihttp://hdl.handle.net/10451/49886
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relationDo miRNAs and TAL1 crosstalk? New insights into the regulation and function of a major T-cell oncogene
dc.relation.publisherversionhttps://www.nature.com/srep/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleMiR-146b negatively regulates migration and delays progression of T-cell acute lymphoblastic leukemiapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberPTDC/BIM-ONC/1548/2012
oaire.awardTitleDo miRNAs and TAL1 crosstalk? New insights into the regulation and function of a major T-cell oncogene
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIM-ONC%2F1548%2F2012/PT
oaire.citation.issue1pt_PT
oaire.citation.titleScientific Reportspt_PT
oaire.citation.volume6pt_PT
oaire.fundingStream3599-PPCDT
person.familyNameFragoso
person.familyNameCarvalho
person.familyNameEnguita
person.familyNameBarata
person.givenNameRita
person.givenNameTânia
person.givenNameFrancisco J.
person.givenNameJoão
person.identifier173306
person.identifier.ciencia-id261B-665F-73EE
person.identifier.ciencia-id4C10-5743-02F8
person.identifier.ciencia-idB215-8D49-3218
person.identifier.orcid0000-0002-9206-1964
person.identifier.orcid0000-0002-5283-5013
person.identifier.orcid0000-0002-8072-8557
person.identifier.orcid0000-0002-4826-8976
person.identifier.ridJ-3656-2013
person.identifier.ridA-2347-2009
person.identifier.ridD-9181-2015
person.identifier.scopus-author-id57210655467
person.identifier.scopus-author-id25653983600
person.identifier.scopus-author-id6602119231
person.identifier.scopus-author-id7006937224
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication45ef496f-867f-4009-b688-3cb1f7395df4
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