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

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dc.contributor.authorMendaza, Saioa
dc.contributor.authorFernández-Irigoyen, Joaquín
dc.contributor.authorSantamaría, Enrique
dc.contributor.authorArozarena, Imanol
dc.contributor.authorGuerrero-Setas, David
dc.contributor.authorZudaire, Tamara
dc.contributor.authorGuarch, Rosa
dc.contributor.authorVidal, August
dc.contributor.authorSalas, José-Santos
dc.contributor.authorMatias-Guiu, Xavier
dc.contributor.authorAusín, Karina
dc.contributor.authorGil, Carmen
dc.contributor.authorHernández-Alcoceba, Rubén
dc.contributor.authorMartín-Sánchez, Esperanza
dc.date.accessioned2021-11-29T11:53:04Z
dc.date.available2021-11-29T11:53:04Z
dc.date.issued2021
dc.description.abstractNo 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.ca_ES
dc.description.sponsorshipThis research was funded by the Health Department of the Navarre Government (Grant number 21/11), the Navarre Breast Cancer Patients’ Association (SARAY), and the “Proof of concept project on proteomic research” from Proteored (Grant number ProteoRed-0000029). The Proteomics Unit of Navarrabiomed is a member of Proteored, PRB3-ISCIII, and is supported by grant PT17/0019/009, of the PE I + D + I 2013-2016 funded by ISCIII and ERDF. S.M. was a recipient of a predoctoral grant from the Public University of Navarre. I.A. was supported by Miguel Servet contract CP15/00176 from the Instituto de Salud Carlos III-FEDER. E.M.-S. was a recipient of a fellowship from the Spanish Ministry of Science, Innovation, and Universities (PTA2015-11895-I)ca_ES
dc.identifier.doihttps://doi.org/10.3390/cancers13071739
dc.identifier.issn2072-6694
dc.identifier.urihttp://hdl.handle.net/10459.1/72441
dc.language.isoengca_ES
dc.publisherMDPIca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.3390/cancers13071739ca_ES
dc.relation.ispartofCancers, 2021, vol. 13, núm. 7, 1739ca_ES
dc.rightscc-by (c) Mendaza et al., 2021ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectmiR-877-3pca_ES
dc.subjectZNF177ca_ES
dc.subjectTherapeutic targetca_ES
dc.subjectPredictive biomarkerca_ES
dc.subjectCCT3ca_ES
dc.subjectTCP-1ca_ES
dc.subjectCytoskeletal protein foldingca_ES
dc.subjectSquamous cell carcinoma of the cervixca_ES
dc.titleUnderstanding the Molecular Mechanism of miR-877-3p Could Provide Potential Biomarkers and Therapeutic Targets in Squamous Cell Carcinoma of the Cervixca_ES
dc.typeinfo:eu-repo/semantics/articleca_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersionca_ES
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