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Anticancer Drugs ; 33(1): e700-e710, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-34845164

RESUMEN

Breast cancer is a frequent tumor threatening the health of women. Circular RNAs (circRNAs) play vital roles in cancer progression and chemoresistance. Herein, we mainly investigate the role and potential mechanism of circRNA ataxin 7 (circATXN7; circ_0066436) in breast cancer. RNA expression levels were detected via quantitative real-time PCR (qPCR), western blot and immunohistochemistry. Cell viability and half inhibitory concentration (IC50) of doxorubicin were assessed by cell counting kit-8 (CCK-8) method. Cell proliferation, migration and invasion were determined by CCK-8, 5-ethynyl-2'-deoxyuridine, colony formation and transwell assays. The binding relationship between microRNA-149-5p (miR-149-5p) and circATXN7 or homeobox A11 (HOXA11) was validated via dual-luciferase reporter assay and RNA immunoprecipitation assay. Xenograft assay was conducted to analyze the effect of circATXN7 on doxorubicin resistance of breast cancer. CircATXN7 and HOXA11 levels were enhanced, whereas miR-149-5p level was declined in breast cancer tissues and cells. CircATXN7 silencing suppressed breast cancer development and doxorubicin resistance. Additionally, circATXN7 upregulated HOXA11 via absorbing miR-149-5p, thereby inducing breast cancer cell progression and reducing doxorubicin sensitivity. Besides, depletion of circATXN7 enhanced doxorubicin sensitivity in vivo. Interference of circATXN7 inhibited breast cancer progression and doxorubicin resistance via mediating miR-149-5p/HOXA11 axis, which might provide a possible biomarker for breast cancer therapy.


Asunto(s)
Ataxina-7/farmacología , Neoplasias de la Mama/patología , Resistencia a Antineoplásicos/efectos de los fármacos , Proteínas de Homeodominio/efectos de los fármacos , MicroARNs/efectos de los fármacos , ARN Circular/farmacología , Animales , Neoplasias de la Mama/mortalidad , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Pronóstico , Unión Proteica/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
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