Mostrar el registro sencillo del ítem

dc.contributor.authorPatiño Mercau, Juan Rodrigo
dc.contributor.authorAndrades, Alvaro
dc.contributor.authorMaria S., Benitez‑Cantos
dc.contributor.authorRodríguez Lara, María Isabel 
dc.contributor.authorÁlvarez Pérez, Juan Carlos
dc.contributor.authorCuadros Celorrio, Marta Eugenia 
dc.contributor.authorMedina Vico, Pedro Pablo 
dc.date.accessioned2023-05-17T07:45:16Z
dc.date.available2023-05-17T07:45:16Z
dc.date.issued2023-03-20
dc.identifier.citationPatiño‑Mercau et al. BCL7A is silenced by hypermethylation to promote acute myeloid leukemia. Biomarker Research (2023) 11:32. [https://doi.org/10.1186/s40364‑023‑00472‑x]es_ES
dc.identifier.urihttps://hdl.handle.net/10481/81598
dc.descriptionThe online version contains supplementary material available at https:// doi. org/ 10. 1186/ s40364‑ 023‑ 00472‑x. Additional file 1: Supplementary Figure 1. Diagram displaying CpG‑ methylation status around the BCL7A TSS. Genomic DNA from the NB4 cell line was subjected to bisulfite conversion and used for subsequent TA‑ cloning. Supplementary Figure 2. Schematic representation of the differ‑ ent lentiviral plasmids used in the experimental procedures. The specific region of the long isoform of BCL7A is colored in blue. Supplementary Figure 3. Western blot including the Decitabine (DAC) treatment over the NB4 cell line shown in Fig. 2c. Supplementary Figure 4. Protein‑protein interactions between BCL7A and SMARCA4 as determined by Mashtalir et al (2020). Supplementary Figure 5. DepMap AML cell lines collection data showing BCL7A Methylation Fraction (1kb upstream TSS) vs BCL7Aex‑ pression level. NB4 and M07e are marked. Supplementary Figure 6. Competition cell growth effect of BCL7A expression restoration on in vitro proliferation. Supplementary Table 1. Additional file 2: Supplementary Table 2. Differential expression analysis resultses_ES
dc.descriptionP.P.M.’s laboratory is funded by Consejería de Universidad, Investigación e Innovación de la Junta de Andalucía and FEDER (P20‑00688), Aula de Investigación sobre la Leucemia infantil: Heroes contra la Leucemia, the Ministry of Science and Innovation of Spain (grant PID2021‑126111OB‑I00), Junta de Andalucía (grants PIGE‑0440–2019, PI‑0135–2020), the University of Granada (grants B‑CTS‑126‑UGR18, B‑CTS‑480‑UGR20, and E‑CTS‑304‑UGR20), and the Spanish Association for Cancer Research (LABORATORY‑AECC‑2018). J.R.P‑M, A.A, and M.S.B‑C were supported by fellowships FPU18/03709, FPU17/00067, and FPU19/00576 respectively funded by the Spanish Ministry of Science, Innovation and Universitieses_ES
dc.description.abstractBackground Recent massive sequencing studies have revealed that SWI/SNF complexes are among the most fre‑ quently altered functional entities in solid tumors. However, the role of SWI/SNF in acute myeloid leukemia is poorly understood. To date, SWI/SNF complexes are thought to be oncogenic in AML or, at least, necessary to support leuke‑ mogenesis. However, mutation patterns in SWI/SNF genes in AML are consistent with a tumor suppressor role. Here, we study the SWI/SNF subunit BCL7A, which has been found to be recurrently mutated in lymphomas, but whose role in acute myeloid malignancies is currently unknown. Methods Data mining and bioinformatic approaches were used to study the mutational status of BCL7A and the correlation between BCL7A expression and promoter hypermethylation. Methylation‑specific PCR, bisulfite sequenc‑ ing, and 5‑aza‑2’‑deoxycytidine treatment assays were used to determine if BCL7A expression was silenced due to promoter hypermethylation. Cell competition assays after BCL7A expression restoration were used to assess the role of BCL7A in AML cell line models. Differential expression analysis was performed to determine pathways and genes altered after BCL7A expression restoration. To establish the role of BCL7A in tumor development in vivo, tumor growth was compared between BCL7A‑expressing and non‑expressing mouse xenografts using in vivo fluorescence imaging. Results BCL7A expression was inversely correlated with promoter methylation in three external cohorts: TCGA‑LAML (N = 160), TARGET‑AML (N = 188), and Glass et al. (2017) (N = 111). The AML‑derived cell line NB4 silenced the BCL7A expression via promoter hypermethylation. Ectopic BCL7A expression in AML cells decreased their competitive ability compared to control cells. Additionally, restoration of BCL7A expression reduced tumor growth in an NB4 mouse xenograft model. Also, differential expression analysis found that BCL7A restoration altered cell cycle pathways and modified significantly the expression of genes like HMGCS1, H1-0, and IRF7 which can help to explain its tumor sup‑ pressor role in AML. Conclusions BCL7A expression is silenced in AML by promoter methylation. In addition, restoration of BCL7A expres‑ sion exerts tumor suppressor activity in AML cell lines and xenograft models.es_ES
dc.description.sponsorshipConsejería de Universidad, Investigación e Innovación de la Junta de Andalucía and FEDER (P20‑00688)es_ES
dc.description.sponsorshipMinistry of Science and Innovation of Spain (grant PID2021‑126111OB‑I00)es_ES
dc.description.sponsorshipJunta de Andalucía (grants PIGE‑0440–2019, PI‑0135–2020)es_ES
dc.description.sponsorshipUniversity of Granada (B‑CTS‑126‑UGR18, B‑CTS‑480‑UGR20, E‑CTS‑304‑UGR20)es_ES
dc.description.sponsorshipSpanish Association for Cancer Research (LABORATORY‑AECC‑2018)es_ES
dc.description.sponsorshipSpanish Ministry of Science, Innovation and Universities FPU18/03709, FPU17/00067, FPU19/00576es_ES
dc.language.isoenges_ES
dc.publisherSpringer Naturees_ES
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectSWI/SNF complexes_ES
dc.subjectAMLes_ES
dc.subjectTumor suppressoes_ES
dc.subjectDNA hypermethylationes_ES
dc.titleBCL7A is silenced by hypermethylation to promote acute myeloid leukemiaes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES
dc.identifier.doi10.1186/s40364-023-00472-x
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones_ES


Ficheros en el ítem

[PDF]

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem

Atribución 4.0 Internacional
Excepto si se señala otra cosa, la licencia del ítem se describe como Atribución 4.0 Internacional