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

Autor: Laura Tatiana Pelegrina, Antonella Rosario Ramona Cáceres, Darío Cuello-Carrión, María de los Ángeles Sanhueza, Cristina Elisa Rodriguez, Myriam Raquel Laconi
Rok vydání: 2020
Předmět:
0301 basic medicine
endocrine system diseases
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Apoptosis
Pregnanolone
Medicina Clínica
Carcinoma
Ovarian Epithelial
Biochemistry
Oncología
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Ovarian carcinoma
Tumor Cells
Cultured
NEUROSTEROIDS
Migration
Progesterone
Tumor Stem Cell Assay
Ovarian Neoplasms
PROLIFERATION
CANCER
medicine.anatomical_structure
030220 oncology & carcinogenesis
Disease Progression
5α-pregnanes
Molecular Medicine
Female
Clonogenic capacity
CIENCIAS MÉDICAS Y DE LA SALUD
Neuroactive steroid
Cell Survival
Caspase 3
Ovary
03 medical and health sciences
medicine
Humans
Clonogenic assay
Molecular Biology
Cell Proliferation
Tumorigenic
business.industry
Allopregnanolone
Cancer
Cell Biology
medicine.disease
030104 developmental biology
chemistry
OVARY
Cancer research
Ovarian cancer
business
Zdroj: UMaza Digital
Universidad Maza
instacron:UMAZA
ISSN: 0960-0760
DOI: 10.1016/j.jsbmb.2019.105492
Popis: 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. Fil: Pelegrina, Laura Tatiana. Universidad "Juan Agustín Maza"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad de Mendoza. Facultad de Ciencias Médicas; Argentina Fil: Sanhueza, María de Los Ángeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Cáceres Gimenez, Antonella Rosario Ramona. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad de Mendoza. Facultad de Ciencias Médicas; Argentina. Universidad "Juan Agustín Maza"; Argentina Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Rodríguez, Cristina Elisa. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina Fil: Laconi, Myriam Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad de Mendoza. Facultad de Ciencias Médicas; Argentina
Databáze: OpenAIRE
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