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Artículo

Effect of progesterone and first evidence about allopregnanolone action on the progression of epithelial human ovarian cancer cell lines

Pelegrina, Laura TatianaIcon ; Sanhueza, María de Los Ángeles; Cáceres Gimenez, Antonella Rosario RamonaIcon ; Cuello Carrión, Fernando DaríoIcon ; Rodríguez, Cristina ElisaIcon ; Laconi, Myriam RaquelIcon
Fecha de publicación: 10/2019
Editorial: Pergamon-Elsevier Science Ltd
Revista: Journal of Steroid Biochemistry and Molecular Biology
ISSN: 0960-0760
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Oncología

Resumen

Ovarian cancer (OvCa) has the highest morbidity among all gynecologic cancers worldwide, and its distant metastasis is one of main causes for the poor prognosis of OvCa patients. Our previous studies have reported that DAAM1-involved signaling pathways play vital roles in metastasis of breast cancer. However, whether DAAM1 participates in OvCa migration and/or invasion is still unknown. The impact of DAAM1 on cell migration and invasion in OvCa was evaluated by wound healing assay and Boyden chamber assay. The specific miRNA targeting DAAM1 was predicted by bioinformatics methods and verified by dual-luciferase activity assay. The miR208a-5p expression levels in OvCa tissues and the impacts of miR-208a-5p on cell migration and invasion were also assessed, respectively. High expression of DAAM1 was associated with distant metastasis in OvCa. Silence of DAAM1 by siRNA blocked the migration and invasion of OVCAR-3 cells. MiR-208a-5p directly targeted DAAM1 and was shown a decreased expression in metastatic OvCa tissues. Elevated expression of miR-208a-5p inhibited the migration and invasion of OVCAR-3 cell which can be rescued by DAAM1 overexpression. Our data suggest that miR-208-5p/DAAM1 axis participates in OvCa migration and invasion and may be a novel clinical target to limit OvCa metastasis.CT Epithelial Ovarian Cancer (EOC) is associated with dismal survival rates due to the fact that patients are frequently diagnosed at an advanced stage and eventually become resistant to traditional chemotherapeutics. Hence, there is a crucial need for new and innovative therapies. Septin-2, a member of the septin family of GTP binding proteins, has been characterized in EOC for the first time and represents a potential future target. Septin-2 was found to be overexpressed in serous and clear cell human patient tissue compared to benign disease. Stable septin-2 knockdown clones developed in an ovarian cancer cell line exhibited a significant decrease in proliferation rates. Comparative label-free proteomic analysis of septin-2 knockdown cells revealed differential protein expression of pathways associated with the TCA cycle, acetyl CoA, proteasome and spliceosome. Further validation of target proteins indicated that septin-2 plays a predominant role in post-transcriptional and translational modifications as well as cellular metabolism, and suggested the potential novel role of septin-2 in promoting EOC tumorigenesis through these mechanisms.
Palabras clave: OVARY , CANCER , NEUROSTEROIDS , PROLIFERATION
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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/110467
URL: https://linkinghub.elsevier.com/retrieve/pii/S0960076019301013
DOI: https://doi.org/10.1016/j.jsbmb.2019.105492
Colecciones
Articulos(IMBECU)
Articulos de INST. DE MEDICINA Y BIO. EXP. DE CUYO
Citación
Pelegrina, Laura Tatiana; Sanhueza, María de Los Ángeles; Cáceres Gimenez, Antonella Rosario Ramona; Cuello Carrión, Fernando Darío; Rodríguez, Cristina Elisa; et al.; Effect of progesterone and first evidence about allopregnanolone action on the progression of epithelial human ovarian cancer cell lines; Pergamon-Elsevier Science Ltd; Journal of Steroid Biochemistry and Molecular Biology; 196; 10-2019; 1-7
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