Understanding the Molecular Mechanism of miR-877-3p Could Provide Potential Biomarkers and Therapeutic Targets in Squamous Cell Carcinoma of the Cervix

Cervical cancer (CC) is managed mainly using subjective and conventional methods. Research about the molecular mechanisms of micro-RNA-877-3p (miR-877-3p) in other cancer types revealed that it interacts with events that are important for CC. Our aim was to understand the role of miR-877-3p in CC. W...

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Autores: Mendaza, Saioa, Fernández Irigoyen, Joaquín, Santamaría, Enrique, Arozarena, Imanol, Guerrero-Setas, David, Zudaire, Tamara, Guarch, Rosa, Vidal-Bel, August, Salas, José Santos, Matias-Guiu, Xavier, 1958-, Ausín, Karina, Gil, Carmen, Hernández Alcoceba, Rubén, Martín Sánchez, Esperanza
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/176790
Acceso en línea:https://hdl.handle.net/2445/176790
Access Level:acceso abierto
Palabra clave:Càncer de coll uterí
Marcadors bioquímics
Cervix cancer
Biochemical markers
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spelling Understanding the Molecular Mechanism of miR-877-3p Could Provide Potential Biomarkers and Therapeutic Targets in Squamous Cell Carcinoma of the CervixMendaza, SaioaFernández Irigoyen, JoaquínSantamaría, EnriqueArozarena, ImanolGuerrero-Setas, DavidZudaire, TamaraGuarch, RosaVidal-Bel, AugustSalas, José SantosMatias-Guiu, Xavier, 1958-Ausín, KarinaGil, CarmenHernández Alcoceba, RubénMartín Sánchez, EsperanzaCàncer de coll uteríMarcadors bioquímicsCervix cancerBiochemical markersCervical cancer (CC) is managed mainly using subjective and conventional methods. Research about the molecular mechanisms of micro-RNA-877-3p (miR-877-3p) in other cancer types revealed that it interacts with events that are important for CC. Our aim was to understand the role of miR-877-3p in CC. We observed that it was overexpressed in cervical tumors compared with benign lesions, and that it promoted CC cell migration and invasion by modulating cytoskeletal protein folding, which potentiated the effects caused by paclitaxel, one of the most common therapeutic drugs used in CC. We demonstrated a functional link between miR-877-3p and one of its predicted targets, ZNF177. The expression and subcellular location of ZNF177 objectively distinguished two CC entities and predicted poor outcome in the most aggressive form. Therefore, the understanding of the molecular mechanisms driven by miR-877-3p provides useful tools for CC clinical management, currently lacking of molecular biomarkers and targeted therapies. No therapeutic targets and molecular biomarkers are available in cervical cancer (CC) management. In other cancer types, micro-RNA-877-3p (miR-877-3p) has been associated with events relevant for CC development. Thus, we aimed to determine miR-877-3p role in CC. miR-877-3p levels were examined by quantitative-PCR in 117 cervical lesions and tumors. Effects on CC cell proliferation, migration, and invasion were evaluated upon anti-miR-877-3p transfection. miR-877-3p dependent molecular mechanism was comprehensively explored by proteomics, dual-luciferase reporter assay, western blot, and immunohistochemistry. Cervical tumors expressed higher miR-877-3p levels than benign lesions. miR-877-3p promoted CC cell migration and invasion, at least partly by modulating cytoskeletal protein folding through the chaperonin-containing T-complex protein 1 complex. Notably, miR-877-3p silencing synergized with paclitaxel. Interestingly, miR-877-3p downregulated the levels of an in silico-predicted target, ZNF177, whose expression and subcellular location significantly distinguished high-grade squamous intraepithelial lesions (HSILs) and squamous cell carcinomas of the cervix (SCCCs). Cytoplasmic ZNF177 was significantly associated with worse progression-free survival in SCCC. Our results suggest that: (i) miR-877-3p is a potential therapeutic target whose inhibition improves paclitaxel effects; (ii) the expression and location of its target ZNF177 could be diagnostic biomarkers between HSIL and SCCC; and (iii) cytoplasmic ZNF177 is a poor-prognosis biomarker in SCCC.MDPI2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/176790Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3390/cancers13071739Cancers, 2021, vol. 13, num. 7https://doi.org/10.3390/cancers13071739cc by (c) Mendaza et al., 2021http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1767902026-05-27T06:46:51Z
dc.title.none.fl_str_mv Understanding the Molecular Mechanism of miR-877-3p Could Provide Potential Biomarkers and Therapeutic Targets in Squamous Cell Carcinoma of the Cervix
title Understanding the Molecular Mechanism of miR-877-3p Could Provide Potential Biomarkers and Therapeutic Targets in Squamous Cell Carcinoma of the Cervix
spellingShingle Understanding the Molecular Mechanism of miR-877-3p Could Provide Potential Biomarkers and Therapeutic Targets in Squamous Cell Carcinoma of the Cervix
Mendaza, Saioa
Càncer de coll uterí
Marcadors bioquímics
Cervix cancer
Biochemical markers
title_short Understanding the Molecular Mechanism of miR-877-3p Could Provide Potential Biomarkers and Therapeutic Targets in Squamous Cell Carcinoma of the Cervix
title_full Understanding the Molecular Mechanism of miR-877-3p Could Provide Potential Biomarkers and Therapeutic Targets in Squamous Cell Carcinoma of the Cervix
title_fullStr Understanding the Molecular Mechanism of miR-877-3p Could Provide Potential Biomarkers and Therapeutic Targets in Squamous Cell Carcinoma of the Cervix
title_full_unstemmed Understanding the Molecular Mechanism of miR-877-3p Could Provide Potential Biomarkers and Therapeutic Targets in Squamous Cell Carcinoma of the Cervix
title_sort Understanding the Molecular Mechanism of miR-877-3p Could Provide Potential Biomarkers and Therapeutic Targets in Squamous Cell Carcinoma of the Cervix
dc.creator.none.fl_str_mv Mendaza, Saioa
Fernández Irigoyen, Joaquín
Santamaría, Enrique
Arozarena, Imanol
Guerrero-Setas, David
Zudaire, Tamara
Guarch, Rosa
Vidal-Bel, August
Salas, José Santos
Matias-Guiu, Xavier, 1958-
Ausín, Karina
Gil, Carmen
Hernández Alcoceba, Rubén
Martín Sánchez, Esperanza
author Mendaza, Saioa
author_facet Mendaza, Saioa
Fernández Irigoyen, Joaquín
Santamaría, Enrique
Arozarena, Imanol
Guerrero-Setas, David
Zudaire, Tamara
Guarch, Rosa
Vidal-Bel, August
Salas, José Santos
Matias-Guiu, Xavier, 1958-
Ausín, Karina
Gil, Carmen
Hernández Alcoceba, Rubén
Martín Sánchez, Esperanza
author_role author
author2 Fernández Irigoyen, Joaquín
Santamaría, Enrique
Arozarena, Imanol
Guerrero-Setas, David
Zudaire, Tamara
Guarch, Rosa
Vidal-Bel, August
Salas, José Santos
Matias-Guiu, Xavier, 1958-
Ausín, Karina
Gil, Carmen
Hernández Alcoceba, Rubén
Martín Sánchez, Esperanza
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer de coll uterí
Marcadors bioquímics
Cervix cancer
Biochemical markers
topic Càncer de coll uterí
Marcadors bioquímics
Cervix cancer
Biochemical markers
description Cervical cancer (CC) is managed mainly using subjective and conventional methods. Research about the molecular mechanisms of micro-RNA-877-3p (miR-877-3p) in other cancer types revealed that it interacts with events that are important for CC. Our aim was to understand the role of miR-877-3p in CC. We observed that it was overexpressed in cervical tumors compared with benign lesions, and that it promoted CC cell migration and invasion by modulating cytoskeletal protein folding, which potentiated the effects caused by paclitaxel, one of the most common therapeutic drugs used in CC. We demonstrated a functional link between miR-877-3p and one of its predicted targets, ZNF177. The expression and subcellular location of ZNF177 objectively distinguished two CC entities and predicted poor outcome in the most aggressive form. Therefore, the understanding of the molecular mechanisms driven by miR-877-3p provides useful tools for CC clinical management, currently lacking of molecular biomarkers and targeted therapies. No therapeutic targets and molecular biomarkers are available in cervical cancer (CC) management. In other cancer types, micro-RNA-877-3p (miR-877-3p) has been associated with events relevant for CC development. Thus, we aimed to determine miR-877-3p role in CC. miR-877-3p levels were examined by quantitative-PCR in 117 cervical lesions and tumors. Effects on CC cell proliferation, migration, and invasion were evaluated upon anti-miR-877-3p transfection. miR-877-3p dependent molecular mechanism was comprehensively explored by proteomics, dual-luciferase reporter assay, western blot, and immunohistochemistry. Cervical tumors expressed higher miR-877-3p levels than benign lesions. miR-877-3p promoted CC cell migration and invasion, at least partly by modulating cytoskeletal protein folding through the chaperonin-containing T-complex protein 1 complex. Notably, miR-877-3p silencing synergized with paclitaxel. Interestingly, miR-877-3p downregulated the levels of an in silico-predicted target, ZNF177, whose expression and subcellular location significantly distinguished high-grade squamous intraepithelial lesions (HSILs) and squamous cell carcinomas of the cervix (SCCCs). Cytoplasmic ZNF177 was significantly associated with worse progression-free survival in SCCC. Our results suggest that: (i) miR-877-3p is a potential therapeutic target whose inhibition improves paclitaxel effects; (ii) the expression and location of its target ZNF177 could be diagnostic biomarkers between HSIL and SCCC; and (iii) cytoplasmic ZNF177 is a poor-prognosis biomarker in SCCC.
publishDate 2021
dc.date.none.fl_str_mv 2021
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/2445/176790
url https://hdl.handle.net/2445/176790
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/cancers13071739
Cancers, 2021, vol. 13, num. 7
https://doi.org/10.3390/cancers13071739
dc.rights.none.fl_str_mv cc by (c) Mendaza et al., 2021
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Mendaza et al., 2021
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 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 (Patologia i Terapèutica Experimental)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301629

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