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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| Övriga upphov: | , , , , , , , , , , , , , , , , |
| 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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| _version_ | 1868889970384568320 |
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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 |