TGF-β/SMAD Pathway Is Modulated by miR-26b-5p: Another Piece in the Puzzle of Chronic Lymphocytic Leukemia Progression

Clinical and molecular heterogeneity are hallmarks of chronic lymphocytic leukemia (CLL), a neoplasm characterized by accumulation of mature and clonal long-lived CD5 + B-lymphocytes. Mutational status of the IgHV gene of leukemic clones is a powerful prognostic tool in CLL, and it is well establish...

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Huvudupphov: Marquez, María Elena (author)
Övriga upphov: Sernbo, Sandra (author), Payque, Eugenia (author), Uría, Rita (author), Tosar, Juan Pablo (author), Querol, Juliana (author), Berca, Catalina (author), Uriepero, Angimar (author), Prieto, Daniel (author), Alvarez-Saravia, Diego (author), Oliver, Carolina (author), Irigoin, Victoria (author), Dos Santos, Gimena (author), Guillermo, Cecilia (author), Landoni, Ana Inés (author), Navarrete, Marcelo (author), Palacios, Florencia (author), Oppezzo, Pablo (author)
Materialtyp: article
Språk:engelska
Utgiven: 2022
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Länkar:https://hdl.handle.net/20.500.12381/3865
https://doi.org/10.3390/cancers14071676
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author Marquez, María Elena
author2 Sernbo, Sandra
Payque, Eugenia
Uría, Rita
Tosar, Juan Pablo
Querol, Juliana
Berca, Catalina
Uriepero, Angimar
Prieto, Daniel
Alvarez-Saravia, Diego
Oliver, Carolina
Irigoin, Victoria
Dos Santos, Gimena
Guillermo, Cecilia
Landoni, Ana Inés
Navarrete, Marcelo
Palacios, Florencia
Oppezzo, Pablo
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author_browse Alvarez-Saravia, Diego
Berca, Catalina
Dos Santos, Gimena
Guillermo, Cecilia
Irigoin, Victoria
Landoni, Ana Inés
Marquez, María Elena
Navarrete, Marcelo
Oliver, Carolina
Oppezzo, Pablo
Palacios, Florencia
Payque, Eugenia
Prieto, Daniel
Querol, Juliana
Sernbo, Sandra
Tosar, Juan Pablo
Uriepero, Angimar
Uría, Rita
author_facet Marquez, María Elena
Sernbo, Sandra
Payque, Eugenia
Uría, Rita
Tosar, Juan Pablo
Querol, Juliana
Berca, Catalina
Uriepero, Angimar
Prieto, Daniel
Alvarez-Saravia, Diego
Oliver, Carolina
Irigoin, Victoria
Dos Santos, Gimena
Guillermo, Cecilia
Landoni, Ana Inés
Navarrete, Marcelo
Palacios, Florencia
Oppezzo, Pablo
author_role author
collection IPMON en REDI
dc.creator.none.fl_str_mv Marquez, María Elena
Sernbo, Sandra
Payque, Eugenia
Uría, Rita
Tosar, Juan Pablo
Querol, Juliana
Berca, Catalina
Uriepero, Angimar
Prieto, Daniel
Alvarez-Saravia, Diego
Oliver, Carolina
Irigoin, Victoria
Dos Santos, Gimena
Guillermo, Cecilia
Landoni, Ana Inés
Navarrete, Marcelo
Palacios, Florencia
Oppezzo, Pablo
dc.date.none.fl_str_mv 2022-03-25
2025-02-13T16:19:10Z
2025-02-13T16:19:10Z
dc.identifier.none.fl_str_mv Marquez, M.E.; Sernbo, S.; Payque, E.; Uria, R.; Tosar, J.P.; Querol, J.; Berca, C.; Uriepero, A.; Prieto, D.; Alvarez-Saravia, D.; et al. TGF-β/SMAD Pathway Is Modulated by miR-26b-5p: Another Piece in the Puzzle of Chronic Lymphocytic Leukemia Progression. Cancers 2022, 14, 1676. https:// doi.org/10.3390/cancers14071676
https://hdl.handle.net/20.500.12381/3865
FSGSK_1_2017_1_146663
https://doi.org/10.3390/cancers14071676
dc.language.none.fl_str_mv eng
dc.publisher.none.fl_str_mv MDPI
dc.relation.none.fl_str_mv https://hdl.handle.net/20.500.12381/3867
https://hdl.handle.net/20.500.12381/3868
https://hdl.handle.net/20.500.12381/3869
https://hdl.handle.net/20.500.12381/3870
https://hdl.handle.net/20.500.12381/5392
https://sisbibliotecas.ort.edu.uy/bib/93863
dc.rights.none.fl_str_mv Acceso abierto
info:eu-repo/semantics/openAccess
Reconocimiento-NoComercial 4.0 Internacional. (CC BY-NC)
dc.source.none.fl_str_mv Cancers
reponame:IPMON en REDI
instname:Institut Pasteur de Montevideo
instacron:Institut Pasteur de Montevideo
dc.subject.none.fl_str_mv Cáncer
Inmunología
Ciencias Naturales y Exactas
Ciencias Biológicas
Bioquímica y Biología Molecular
dc.title.none.fl_str_mv TGF-β/SMAD Pathway Is Modulated by miR-26b-5p: Another Piece in the Puzzle of Chronic Lymphocytic Leukemia Progression
dc.type.none.fl_str_mv Artículo
info:eu-repo/semantics/article
Publicado
info:eu-repo/semantics/publishedVersion
description Clinical and molecular heterogeneity are hallmarks of chronic lymphocytic leukemia (CLL), a neoplasm characterized by accumulation of mature and clonal long-lived CD5 + B-lymphocytes. Mutational status of the IgHV gene of leukemic clones is a powerful prognostic tool in CLL, and it is well established that unmutated CLLs (U-CLLs) have worse evolution than mutated cases. Nevertheless, progression and treatment requirement of patients can evolve independently from the mutational status. Microenvironment signaling or epigenetic changes partially explain this different behavior. Thus, we think that detailed characterization of the miRNAs landscape from patients with different clinical evolution could facilitate the understanding of this heterogeneity. Since miRNAs are key players in leukemia pathogenesis and evolution, we aim to better characterize different CLL behaviors by comparing the miRNome of clinically progressive U-CLLs vs. stable U-CLLs. Our data show up-regulation of miR-26b-5p, miR-106b-5p, and miR-142-5p in progressive cases and indicate a key role for miR-26b-5p during CLL progression. Specifically, up-regulation of miR-26b-5p in CLL cells blocks TGF-β/SMAD pathway by down-modulation of SMAD-4, resulting in lower expression of p21-Cip1 kinase inhibitor and higher expression of c-Myc oncogene. This work describes a new molecular mechanism linking CLL progression with TGF-β modulation and proposes an alternative strategy to explore in CLL therapy.
eu_rights_str_mv openAccess
format article
id anni_19746d64eabe6040b3ec2e76955cd4c2
identifier_str_mv Marquez, M.E.; Sernbo, S.; Payque, E.; Uria, R.; Tosar, J.P.; Querol, J.; Berca, C.; Uriepero, A.; Prieto, D.; Alvarez-Saravia, D.; et al. TGF-β/SMAD Pathway Is Modulated by miR-26b-5p: Another Piece in the Puzzle of Chronic Lymphocytic Leukemia Progression. Cancers 2022, 14, 1676. https:// doi.org/10.3390/cancers14071676
FSGSK_1_2017_1_146663
instacron_str Institut Pasteur de Montevideo
institution Institut Pasteur de Montevideo
instname_str Institut Pasteur de Montevideo
language eng
network_acronym_str anni
network_name_str oai-lr-anni
oai_identifier_str oai:redi.anii.org.uy:20.500.12381/3865
publishDate 2022
publishDateSort 2022
publisher.none.fl_str_mv MDPI
reponame_str IPMON en REDI
repository.mail.fl_str_mv
repository.name.fl_str_mv
repository_id_str
rights_invalid_str_mv Acceso abierto
Reconocimiento-NoComercial 4.0 Internacional. (CC BY-NC)
spelling TGF-β/SMAD Pathway Is Modulated by miR-26b-5p: Another Piece in the Puzzle of Chronic Lymphocytic Leukemia ProgressionMarquez, María ElenaSernbo, SandraPayque, EugeniaUría, RitaTosar, Juan PabloQuerol, JulianaBerca, CatalinaUriepero, AngimarPrieto, DanielAlvarez-Saravia, DiegoOliver, CarolinaIrigoin, VictoriaDos Santos, GimenaGuillermo, CeciliaLandoni, Ana InésNavarrete, MarceloPalacios, FlorenciaOppezzo, PabloCáncerInmunologíaCiencias Naturales y ExactasCiencias BiológicasBioquímica y Biología MolecularClinical and molecular heterogeneity are hallmarks of chronic lymphocytic leukemia (CLL), a neoplasm characterized by accumulation of mature and clonal long-lived CD5 + B-lymphocytes. Mutational status of the IgHV gene of leukemic clones is a powerful prognostic tool in CLL, and it is well established that unmutated CLLs (U-CLLs) have worse evolution than mutated cases. Nevertheless, progression and treatment requirement of patients can evolve independently from the mutational status. Microenvironment signaling or epigenetic changes partially explain this different behavior. Thus, we think that detailed characterization of the miRNAs landscape from patients with different clinical evolution could facilitate the understanding of this heterogeneity. Since miRNAs are key players in leukemia pathogenesis and evolution, we aim to better characterize different CLL behaviors by comparing the miRNome of clinically progressive U-CLLs vs. stable U-CLLs. Our data show up-regulation of miR-26b-5p, miR-106b-5p, and miR-142-5p in progressive cases and indicate a key role for miR-26b-5p during CLL progression. Specifically, up-regulation of miR-26b-5p in CLL cells blocks TGF-β/SMAD pathway by down-modulation of SMAD-4, resulting in lower expression of p21-Cip1 kinase inhibitor and higher expression of c-Myc oncogene. This work describes a new molecular mechanism linking CLL progression with TGF-β modulation and proposes an alternative strategy to explore in CLL therapy.Institut Pasteur de MontevideoAgencia Nacional de Investigación e InnovaciónAgencia Nacional de Investigación y Desarrollo, Fondecyt, ChileMANMDPI2025-02-13T16:19:10Z2025-02-13T16:19:10Z2022-03-25Artículoinfo:eu-repo/semantics/articlePublicadoinfo:eu-repo/semantics/publishedVersionMarquez, M.E.; Sernbo, S.; Payque, E.; Uria, R.; Tosar, J.P.; Querol, J.; Berca, C.; Uriepero, A.; Prieto, D.; Alvarez-Saravia, D.; et al. TGF-β/SMAD Pathway Is Modulated by miR-26b-5p: Another Piece in the Puzzle of Chronic Lymphocytic Leukemia Progression. Cancers 2022, 14, 1676. https:// doi.org/10.3390/cancers14071676https://hdl.handle.net/20.500.12381/3865FSGSK_1_2017_1_146663https://doi.org/10.3390/cancers14071676Cancersreponame:IPMON en REDIinstname:Institut Pasteur de Montevideoinstacron:Institut Pasteur de Montevideoenghttps://hdl.handle.net/20.500.12381/3867https://hdl.handle.net/20.500.12381/3868https://hdl.handle.net/20.500.12381/3869https://hdl.handle.net/20.500.12381/3870https://hdl.handle.net/20.500.12381/5392https://sisbibliotecas.ort.edu.uy/bib/93863Acceso abiertoinfo:eu-repo/semantics/openAccessReconocimiento-NoComercial 4.0 Internacional. (CC BY-NC)oai:redi.anii.org.uy:20.500.12381/38652026-06-16T05:20:20Z
spellingShingle TGF-β/SMAD Pathway Is Modulated by miR-26b-5p: Another Piece in the Puzzle of Chronic Lymphocytic Leukemia Progression
Marquez, María Elena
Cáncer
Inmunología
Ciencias Naturales y Exactas
Ciencias Biológicas
Bioquímica y Biología Molecular
status_str publishedVersion
title TGF-β/SMAD Pathway Is Modulated by miR-26b-5p: Another Piece in the Puzzle of Chronic Lymphocytic Leukemia Progression
title_full TGF-β/SMAD Pathway Is Modulated by miR-26b-5p: Another Piece in the Puzzle of Chronic Lymphocytic Leukemia Progression
title_fullStr TGF-β/SMAD Pathway Is Modulated by miR-26b-5p: Another Piece in the Puzzle of Chronic Lymphocytic Leukemia Progression
title_full_unstemmed TGF-β/SMAD Pathway Is Modulated by miR-26b-5p: Another Piece in the Puzzle of Chronic Lymphocytic Leukemia Progression
title_short TGF-β/SMAD Pathway Is Modulated by miR-26b-5p: Another Piece in the Puzzle of Chronic Lymphocytic Leukemia Progression
title_sort TGF-β/SMAD Pathway Is Modulated by miR-26b-5p: Another Piece in the Puzzle of Chronic Lymphocytic Leukemia Progression
topic Cáncer
Inmunología
Ciencias Naturales y Exactas
Ciencias Biológicas
Bioquímica y Biología Molecular
url https://hdl.handle.net/20.500.12381/3865
https://doi.org/10.3390/cancers14071676