NGF/TRKA Decrease miR-145-5p Levels in Epithelial Ovarian Cancer Cells

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dc.contributor.authorGarrido, Maritza P.
dc.contributor.authorTorres, Ignacio
dc.contributor.authorAvila, Alba
dc.contributor.authorChnaiderman, Jonás
dc.contributor.authorValenzuela-Valderrama, Manuel
dc.contributor.authorAramburo, José
dc.contributor.authorOróstica, Lorena
dc.contributor.authorDuran, Eduardo
dc.contributor.authorLobos-González, Lorena
dc.contributor.authorRomero, Carmen
dc.date.accessioned2021-07-14T14:27:02Z
dc.date.available2021-07-14T14:27:02Z
dc.date.issued2020
dc.description.abstractNerve Growth Factor (NGF) and its high-affinity receptor tropomyosin receptor kinase A (TRKA) increase their expression during the progression of epithelial ovarian cancer (EOC), promoting cell proliferation and angiogenesis through several oncogenic proteins, such as c-MYC and vascular endothelial growth factor (VEGF). The expression of these proteins is controlled by microRNAs (miRs), such as miR-145, whose dysregulation has been related to cancer. The aims of this work were to evaluate in EOC cells whether NGF/TRKA decreases miR-145 levels, and the effect of miR-145 upregulation. The levels of miR-145-5p were assessed by qPCR in ovarian biopsies and ovarian cell lines (human ovarian surface epithelial cells (HOSE), A2780 and SKOV3) stimulated with NGF. Overexpression of miR-145 in ovarian cells was used to evaluate cell proliferation, migration, invasion, c-MYC and VEGF protein levels, as well as tumor formation and metastasis in vivo. In EOC samples, miR-145-5p levels were lower than in epithelial ovarian tumors. Overexpression of miR-145 decreased cell proliferation, migration and invasion of EOC cells, changes that were concomitant with the decrease in c-MYC and VEGF protein levels. We observed decreased tumor formation and suppressed metastasis behavior in mice injected with EOC cells that overexpressed miR-145. As expected, ovarian cell lines stimulated with NGF diminished miR-145-5p transcription and abundance. These results suggest that the tumoral effects of NGF/TRKA depend on the regulation of miR-145-5p levels in EOC cells, and that its upregulation could be used as a possible therapeutic strategy for EOC.es
dc.format.extent21 p.es
dc.identifier.citationInternational Journal of Molecular Sciences. 2020, 21(20), 7657es
dc.identifier.urihttps://doi.org/10.3390/ijms21207657es
dc.identifier.urihttp://hdl.handle.net/11447/4173
dc.language.isoenes
dc.subjectmicroRNA-145es
dc.subjectNGFes
dc.subjectTRKAes
dc.subjectEpithelial ovarian canceres
dc.subjectc-MYCes
dc.subjectVEGFes
dc.titleNGF/TRKA Decrease miR-145-5p Levels in Epithelial Ovarian Cancer Cellses
dc.typeArticlees

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