NGF/TRKA Decrease miR-145-5p Levels in Epithelial Ovarian Cancer Cells
Journal
International Journal of Molecular Sciences
ISSN
1422-0067
Date Issued
2020
Author(s)
Maritza P. Garrido
Ignacio Torres
Jonás Chnaiderman
Manuel Valenzuela-Valderrama
José Aramburo
Lorena Oróstica
Eduardo Durán-Jara
Lorena Lobos-Gonzalez
Carmen Romero
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:p>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 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.</jats:p>
Cite this document
Garrido, M. P., Torres, I., Avila, A., Chnaiderman, J., Valenzuela-Valderrama, M., Aramburo, J., Oróstica, L., Durán-Jara, E., Lobos-Gonzalez, L., & Romero, C. (2020). Ngf/trka decrease mir-145-5p levels in epithelial ovarian cancer cells. International Journal of Molecular Sciences, 21(20), 7657. https://doi.org/10.3390/ijms21207657
Subjects
microrna-145
;
ngf
;
trka
;
epithelial ovarian cancer
;
c-myc
;
vegf
;
aged
;
carcinoma
;
cell line, tumor
;
cell movement
;
cell proliferation
;
female
;
humans
;
micrornas
;
middle aged
;
nerve growth factor
;
ovarian neoplasms
;
proto-oncogene proteins c-myc
;
receptor, trka
;
up-regulation
;
vascular endothelial growth factor a
;
microrna 145
;
microrna 145 5p
;
nerve growth factor
;
protein tyrosine kinase a
;
unclassified drug
;
vasculotropin
;
microrna
;
mirn145 microrna, human
;
myc protein
;
nerve growth factor
;
ntrk1 protein, human
;
protein tyrosine kinase a
;
vasculotropin a
;
a2780 cell line
;
animal experiment
;
animal model
;
article
;
ascites
;
carcinogenesis
;
carcinomatous peritonitis
;
cell invasion
;
cell migration
;
cell proliferation
;
cell stimulation
;
computer model
;
controlled study
;
female
;
gene expression level
;
gene overexpression
;
human
;
human cell
;
human tissue
;
in vivo study
;
metastasis
;
mouse
;
nonhuman
;
oncogene c myc
;
ovary carcinoma
;
polymerase chain reaction
;
signal transduction
;
sk-ov-3 cell line
;
transcription termination
;
tumor volume
;
upregulation
;
aged
;
carcinoma
;
cell motion
;
genetics
;
metabolism
;
middle aged
;
ovary tumor
;
pathology
;
tumor cell line
;
upregulation