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

Garrido MP, Torres I, Avila A, Chnaiderman J, Valenzuela-Valderrama M, Aramburo J, Oróstica L, Durán-Jara E, Lobos-Gonzalez L*, Romero C.*

Keywords: epithelial ovarian cancer, c-myc, ngf, vegf, trka, microRNA-145

Abstract

: Nerve 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 cellproliferation and angiogenesis through several oncogenic proteins, such as c-MYC and vascular endothelial growth factor (VEGF). The expression of these proteinsis controlled bymicroRNAs (miRs), such asmiR-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.

Más información

Título de la Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volumen: 16;21(20):7657.
Editorial: MPDi
Fecha de publicación: 2020
Idioma: Ingles
Financiamiento/Sponsor: This work was funded with the grant N◦ 1160139 from the “Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT)”
URL: https://www.mdpi.com/1422-0067/21/20/7657
DOI:

doi: 10.3390/ijms21207657

Notas: ISI Impact Factor::4.556