SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Gain of function in receptor tyrosine kinases type III, KIT, or PDGFRA drives the majority of GIST. Previously, our group reported that silencing of the adaptor molecule SH3 Binding Protein...

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Detalles Bibliográficos
Autores: Proaño Pérez, Elizabeth, Serrano Candelas, Eva, 1982-, Mancia, Cindy, Navinés Ferrer, Arnau, Guerrero, Mario, Martín Andorrà, Margarita
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/192129
Acceso en línea:https://hdl.handle.net/2445/192129
Access Level:acceso abierto
Palabra clave:Cicle cel·lular
Càncer gastrointestinal
Micro RNAs
Factors de transcripció
Cell cycle
Gastrointestinal cancer
MicroRNAs
Transcription factors
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spelling SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal TumorsProaño Pérez, ElizabethSerrano Candelas, Eva, 1982-Mancia, CindyNavinés Ferrer, ArnauGuerrero, MarioMartín Andorrà, MargaritaCicle cel·lularCàncer gastrointestinalMicro RNAsFactors de transcripcióCell cycleGastrointestinal cancerMicroRNAsTranscription factorsGastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Gain of function in receptor tyrosine kinases type III, KIT, or PDGFRA drives the majority of GIST. Previously, our group reported that silencing of the adaptor molecule SH3 Binding Protein 2 (SH3BP2) downregulated KIT and PDGFRA and microphthalmia-associated transcription factor (MITF) levels and reduced tumor growth. This study shows that SH3BP2 silencing also decreases levels of ETV1, a required factor for GIST growth. To dissect the SH3BP2 pathway in GIST cells, we performed a miRNA array in SH3BP2-silenced GIST cell lines. Among the most up-regulated miRNAs, we found miR-1246 and miR-5100 to be predicted to target MITF and ETV1. Overexpression of these miRNAs led to a decrease in MITF and ETV1 levels. In this context, cell viability and cell cycle progression were affected, and a reduction in BCL2 and CDK2 was observed. Interestingly, overexpression of MITF enhanced cell proliferation and significantly rescued the viability of miRNA-transduced cells. Altogether, the KIT-SH3BP2-MITF/ETV1 pathway deserves to be considered in GIST cell survival and proliferation.MDPI2023202320222023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion15 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/192129Articles publicats en revistes (Biomedicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/cancers14246198Cancers, 2022, vol. 14, num. 24, p. 6198https://doi.org/10.3390/cancers14246198cc-by (c) Proaño Pérez, Elisabeth et al., 2022https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1921292026-05-29T05:05:01Z
dc.title.none.fl_str_mv SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal Tumors
title SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal Tumors
spellingShingle SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal Tumors
Proaño Pérez, Elizabeth
Cicle cel·lular
Càncer gastrointestinal
Micro RNAs
Factors de transcripció
Cell cycle
Gastrointestinal cancer
MicroRNAs
Transcription factors
title_short SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal Tumors
title_full SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal Tumors
title_fullStr SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal Tumors
title_full_unstemmed SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal Tumors
title_sort SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal Tumors
dc.creator.none.fl_str_mv Proaño Pérez, Elizabeth
Serrano Candelas, Eva, 1982-
Mancia, Cindy
Navinés Ferrer, Arnau
Guerrero, Mario
Martín Andorrà, Margarita
author Proaño Pérez, Elizabeth
author_facet Proaño Pérez, Elizabeth
Serrano Candelas, Eva, 1982-
Mancia, Cindy
Navinés Ferrer, Arnau
Guerrero, Mario
Martín Andorrà, Margarita
author_role author
author2 Serrano Candelas, Eva, 1982-
Mancia, Cindy
Navinés Ferrer, Arnau
Guerrero, Mario
Martín Andorrà, Margarita
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Cicle cel·lular
Càncer gastrointestinal
Micro RNAs
Factors de transcripció
Cell cycle
Gastrointestinal cancer
MicroRNAs
Transcription factors
topic Cicle cel·lular
Càncer gastrointestinal
Micro RNAs
Factors de transcripció
Cell cycle
Gastrointestinal cancer
MicroRNAs
Transcription factors
description Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Gain of function in receptor tyrosine kinases type III, KIT, or PDGFRA drives the majority of GIST. Previously, our group reported that silencing of the adaptor molecule SH3 Binding Protein 2 (SH3BP2) downregulated KIT and PDGFRA and microphthalmia-associated transcription factor (MITF) levels and reduced tumor growth. This study shows that SH3BP2 silencing also decreases levels of ETV1, a required factor for GIST growth. To dissect the SH3BP2 pathway in GIST cells, we performed a miRNA array in SH3BP2-silenced GIST cell lines. Among the most up-regulated miRNAs, we found miR-1246 and miR-5100 to be predicted to target MITF and ETV1. Overexpression of these miRNAs led to a decrease in MITF and ETV1 levels. In this context, cell viability and cell cycle progression were affected, and a reduction in BCL2 and CDK2 was observed. Interestingly, overexpression of MITF enhanced cell proliferation and significantly rescued the viability of miRNA-transduced cells. Altogether, the KIT-SH3BP2-MITF/ETV1 pathway deserves to be considered in GIST cell survival and proliferation.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/192129
url https://hdl.handle.net/2445/192129
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/cancers14246198
Cancers, 2022, vol. 14, num. 24, p. 6198
https://doi.org/10.3390/cancers14246198
dc.rights.none.fl_str_mv cc-by (c) Proaño Pérez, Elisabeth et al., 2022
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Proaño Pérez, Elisabeth et al., 2022
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 15 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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