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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2021Author
Mendaza, Saioa
Fernández-Irigoyen, Joaquín
Santamaría, Enrique
Arozarena, Imanol
Guerrero-Setas, David
Zudaire, Tamara
Guarch, Rosa
Vidal, August
Salas, José-Santos
Ausín, Karina
Gil, Carmen
Hernández-Alcoceba, Rubén
Martín-Sánchez, Esperanza
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Mendaza, Saioa;
Fernández-Irigoyen, Joaquín;
Santamaría, Enrique;
Arozarena, Imanol;
Guerrero-Setas, David;
Zudaire, Tamara;
...
Martín-Sánchez, Esperanza.
(2021)
.
Understanding the Molecular Mechanism of miR-877-3p Could Provide Potential Biomarkers and Therapeutic Targets in Squamous Cell Carcinoma of the Cervix.
Cancers, 2021, vol. 13, núm. 7, 1739.
https://doi.org/10.3390/cancers13071739.
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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.
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Cancers, 2021, vol. 13, núm. 7, 1739European research projects
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