ΔNp63α suppresses cells invasion by downregulating PKCγ/Rac1 signaling through miR-320a

Autores
Aljagthmi, Amjad A.; Hill, Natasha T.; Cooke, Mariana; Kazanietz, Marcelo Gabriel; Abba, Martín Carlos; Long, Weiwen; Kadakia, Madhavi P.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
ΔNp63α, a member of the p53 family of transcription factors, is overexpressed in a number of cancers and plays a role in proliferation, differentiation, migration, and invasion. ΔNp63α has been shown to regulate several microRNAs that are involved in development and cancer. We identified miRNA miR-320a as a positively regulated target of ΔNp63α. Previous studies have shown that miR-320a is downregulated in colorectal cancer and targets the small GTPase Rac1, leading to a reduction in noncanonical WNT signaling and EMT, thereby inhibiting tumor metastasis and invasion. We showed that miR-320a is a direct target of ΔNp63α. Knockdown of ΔNp63α in HaCaT and A431 cells downregulates miR-320a levels and leads to a corresponding elevation in PKCγ transcript and protein levels. Rac1 phosphorylation at Ser71 was increased in the absence of ΔNp63α, whereas overexpression of ΔNp63α reversed S71 phosphorylation of Rac1. Moreover, increased PKCγ levels, Rac1 phosphorylation and cell invasion observed upon knockdown of ΔNp63α was reversed by either overexpressing miR-320a mimic or Rac1 silencing. Finally, silencing PKCγ or treatment with the PKC inhibitor Gö6976 reversed increased Rac1 phosphorylation and cell invasion observed upon silencing ΔNp63α. Taken together, our data suggest that ΔNp63α positively regulates miR-320a, thereby inhibiting PKCγ expression, Rac1 phosphorylation, and cancer invasion.
Fil: Aljagthmi, Amjad A.. Wright State University; Estados Unidos
Fil: Hill, Natasha T.. Wright State University; Estados Unidos
Fil: Cooke, Mariana. University of Pennsylvania; Estados Unidos
Fil: Kazanietz, Marcelo Gabriel. University of Pennsylvania; Estados Unidos
Fil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Long, Weiwen. Wright State University; Estados Unidos
Fil: Kadakia, Madhavi P.. Wright State University; Estados Unidos
Materia
Dp63
miR320
CANCER
INVASION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/129040
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/129040
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling ΔNp63α suppresses cells invasion by downregulating PKCγ/Rac1 signaling through miR-320aAljagthmi, Amjad A.Hill, Natasha T.Cooke, MarianaKazanietz, Marcelo GabrielAbba, Martín CarlosLong, WeiwenKadakia, Madhavi P.Dp63miR320CANCERINVASIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1ΔNp63α, a member of the p53 family of transcription factors, is overexpressed in a number of cancers and plays a role in proliferation, differentiation, migration, and invasion. ΔNp63α has been shown to regulate several microRNAs that are involved in development and cancer. We identified miRNA miR-320a as a positively regulated target of ΔNp63α. Previous studies have shown that miR-320a is downregulated in colorectal cancer and targets the small GTPase Rac1, leading to a reduction in noncanonical WNT signaling and EMT, thereby inhibiting tumor metastasis and invasion. We showed that miR-320a is a direct target of ΔNp63α. Knockdown of ΔNp63α in HaCaT and A431 cells downregulates miR-320a levels and leads to a corresponding elevation in PKCγ transcript and protein levels. Rac1 phosphorylation at Ser71 was increased in the absence of ΔNp63α, whereas overexpression of ΔNp63α reversed S71 phosphorylation of Rac1. Moreover, increased PKCγ levels, Rac1 phosphorylation and cell invasion observed upon knockdown of ΔNp63α was reversed by either overexpressing miR-320a mimic or Rac1 silencing. Finally, silencing PKCγ or treatment with the PKC inhibitor Gö6976 reversed increased Rac1 phosphorylation and cell invasion observed upon silencing ΔNp63α. Taken together, our data suggest that ΔNp63α positively regulates miR-320a, thereby inhibiting PKCγ expression, Rac1 phosphorylation, and cancer invasion.Fil: Aljagthmi, Amjad A.. Wright State University; Estados UnidosFil: Hill, Natasha T.. Wright State University; Estados UnidosFil: Cooke, Mariana. University of Pennsylvania; Estados UnidosFil: Kazanietz, Marcelo Gabriel. University of Pennsylvania; Estados UnidosFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Long, Weiwen. Wright State University; Estados UnidosFil: Kadakia, Madhavi P.. Wright State University; Estados UnidosNature Publishing Group2019-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/129040Aljagthmi, Amjad A.; Hill, Natasha T.; Cooke, Mariana; Kazanietz, Marcelo Gabriel; Abba, Martín Carlos; et al.; ΔNp63α suppresses cells invasion by downregulating PKCγ/Rac1 signaling through miR-320a; Nature Publishing Group; Cell Death and Disease; 10; 9; 9-2019; 1-141350-90472041-4889CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41419-019-1921-6info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:13Zoai:ri.conicet.gov.ar:11336/129040instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:57:13.328CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv ΔNp63α suppresses cells invasion by downregulating PKCγ/Rac1 signaling through miR-320a
title ΔNp63α suppresses cells invasion by downregulating PKCγ/Rac1 signaling through miR-320a
spellingShingle ΔNp63α suppresses cells invasion by downregulating PKCγ/Rac1 signaling through miR-320a
Aljagthmi, Amjad A.
Dp63
miR320
CANCER
INVASION
title_short ΔNp63α suppresses cells invasion by downregulating PKCγ/Rac1 signaling through miR-320a
title_full ΔNp63α suppresses cells invasion by downregulating PKCγ/Rac1 signaling through miR-320a
title_fullStr ΔNp63α suppresses cells invasion by downregulating PKCγ/Rac1 signaling through miR-320a
title_full_unstemmed ΔNp63α suppresses cells invasion by downregulating PKCγ/Rac1 signaling through miR-320a
title_sort ΔNp63α suppresses cells invasion by downregulating PKCγ/Rac1 signaling through miR-320a
dc.creator.none.fl_str_mv Aljagthmi, Amjad A.
Hill, Natasha T.
Cooke, Mariana
Kazanietz, Marcelo Gabriel
Abba, Martín Carlos
Long, Weiwen
Kadakia, Madhavi P.
author Aljagthmi, Amjad A.
author_facet Aljagthmi, Amjad A.
Hill, Natasha T.
Cooke, Mariana
Kazanietz, Marcelo Gabriel
Abba, Martín Carlos
Long, Weiwen
Kadakia, Madhavi P.
author_role author
author2 Hill, Natasha T.
Cooke, Mariana
Kazanietz, Marcelo Gabriel
Abba, Martín Carlos
Long, Weiwen
Kadakia, Madhavi P.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Dp63
miR320
CANCER
INVASION
topic Dp63
miR320
CANCER
INVASION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv ΔNp63α, a member of the p53 family of transcription factors, is overexpressed in a number of cancers and plays a role in proliferation, differentiation, migration, and invasion. ΔNp63α has been shown to regulate several microRNAs that are involved in development and cancer. We identified miRNA miR-320a as a positively regulated target of ΔNp63α. Previous studies have shown that miR-320a is downregulated in colorectal cancer and targets the small GTPase Rac1, leading to a reduction in noncanonical WNT signaling and EMT, thereby inhibiting tumor metastasis and invasion. We showed that miR-320a is a direct target of ΔNp63α. Knockdown of ΔNp63α in HaCaT and A431 cells downregulates miR-320a levels and leads to a corresponding elevation in PKCγ transcript and protein levels. Rac1 phosphorylation at Ser71 was increased in the absence of ΔNp63α, whereas overexpression of ΔNp63α reversed S71 phosphorylation of Rac1. Moreover, increased PKCγ levels, Rac1 phosphorylation and cell invasion observed upon knockdown of ΔNp63α was reversed by either overexpressing miR-320a mimic or Rac1 silencing. Finally, silencing PKCγ or treatment with the PKC inhibitor Gö6976 reversed increased Rac1 phosphorylation and cell invasion observed upon silencing ΔNp63α. Taken together, our data suggest that ΔNp63α positively regulates miR-320a, thereby inhibiting PKCγ expression, Rac1 phosphorylation, and cancer invasion.
Fil: Aljagthmi, Amjad A.. Wright State University; Estados Unidos
Fil: Hill, Natasha T.. Wright State University; Estados Unidos
Fil: Cooke, Mariana. University of Pennsylvania; Estados Unidos
Fil: Kazanietz, Marcelo Gabriel. University of Pennsylvania; Estados Unidos
Fil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Long, Weiwen. Wright State University; Estados Unidos
Fil: Kadakia, Madhavi P.. Wright State University; Estados Unidos
description ΔNp63α, a member of the p53 family of transcription factors, is overexpressed in a number of cancers and plays a role in proliferation, differentiation, migration, and invasion. ΔNp63α has been shown to regulate several microRNAs that are involved in development and cancer. We identified miRNA miR-320a as a positively regulated target of ΔNp63α. Previous studies have shown that miR-320a is downregulated in colorectal cancer and targets the small GTPase Rac1, leading to a reduction in noncanonical WNT signaling and EMT, thereby inhibiting tumor metastasis and invasion. We showed that miR-320a is a direct target of ΔNp63α. Knockdown of ΔNp63α in HaCaT and A431 cells downregulates miR-320a levels and leads to a corresponding elevation in PKCγ transcript and protein levels. Rac1 phosphorylation at Ser71 was increased in the absence of ΔNp63α, whereas overexpression of ΔNp63α reversed S71 phosphorylation of Rac1. Moreover, increased PKCγ levels, Rac1 phosphorylation and cell invasion observed upon knockdown of ΔNp63α was reversed by either overexpressing miR-320a mimic or Rac1 silencing. Finally, silencing PKCγ or treatment with the PKC inhibitor Gö6976 reversed increased Rac1 phosphorylation and cell invasion observed upon silencing ΔNp63α. Taken together, our data suggest that ΔNp63α positively regulates miR-320a, thereby inhibiting PKCγ expression, Rac1 phosphorylation, and cancer invasion.
publishDate 2019
dc.date.none.fl_str_mv 2019-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/129040
Aljagthmi, Amjad A.; Hill, Natasha T.; Cooke, Mariana; Kazanietz, Marcelo Gabriel; Abba, Martín Carlos; et al.; ΔNp63α suppresses cells invasion by downregulating PKCγ/Rac1 signaling through miR-320a; Nature Publishing Group; Cell Death and Disease; 10; 9; 9-2019; 1-14
1350-9047
2041-4889
CONICET Digital
CONICET
url http://hdl.handle.net/11336/129040
identifier_str_mv Aljagthmi, Amjad A.; Hill, Natasha T.; Cooke, Mariana; Kazanietz, Marcelo Gabriel; Abba, Martín Carlos; et al.; ΔNp63α suppresses cells invasion by downregulating PKCγ/Rac1 signaling through miR-320a; Nature Publishing Group; Cell Death and Disease; 10; 9; 9-2019; 1-14
1350-9047
2041-4889
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/s41419-019-1921-6
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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