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Arch Gynecol Obstet ; 306(5): 1643-1655, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35284960

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have been reported to function as vital regulators in cancers, including triple-negative breast cancer (TNBC). This study aimed to explore the role of circ_0062558 in TNBC. METHODS: The real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to quantify the expressions of circ_0062558, microRNA-876-3p (miR-876-3p), and solute carrier family 1 (neutral amino acid transporter), member 5 (SLC1A5) in TNBC tissues and cells. 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT), thymidine analog 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, wound healing, and Transwell assays were employed for cell phenotype analyses. Protein expression was tested by western blot analysis. Dual-luciferase reporter was used to confirm the association among circ_0062558, miR-876-3p, and SLC1A5 in TNBC. Xenograft experiments were performed to elucidate the function of circ_0062558 in vivo. RESULTS: TNBC tissues and cells showed the higher level of circ_0062558 when compared with control samples. Downregulation of circ_0062558 inhibited proliferation, migration, invasion, and glutamine metabolism, while enhanced apoptosis of TNBC cells, and silencing of circ_0062558 also inhibited the growth of tumor in vivo. MiR-876-3p was confirmed as a target of circ_0062558, and circ_0062558 knockdown repressed TNBC cell malignant behaviors by increasing miR-876-3p. Furthermore, miR-876-3p inhibited malignant behaviors of TNBC cells by down-regulating SLC1A5, a newly identified target of miR-876-3p. CONCLUSION: Circ_0062558 promoted TNBC progression by enhancing proliferation, survival, migration, invasion, and glutamine metabolism via miR-876-3p/SLC1A5 axis, which was helpful for understanding the carcinogenic roles of circ_0062558.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros , MicroRNAs , Neoplasias de Mama Triplo Negativas , Sistema ASC de Transporte de Aminoácidos/genética , Sistema ASC de Transporte de Aminoácidos/metabolismo , Sistemas de Transporte de Aminoácidos Neutros/genética , Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Animais , Brometos/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glutamina/genética , Glutamina/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Antígenos de Histocompatibilidade Menor , RNA Circular/genética , Timidina , Neoplasias de Mama Triplo Negativas/genética
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