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Cell Death Dis ; 13(7): 625, 2022 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-35853854

RESUMEN

Earlier studies have suggested deleted in lymphocytic leukemia 1 (DLEU1), a long non-coding RNA, is a prognostic biomarker for breast cancer. Here we explored the malignant behaviors and underlying mechanisms regulated by DLEU1 in breast cancer. We demonstrated that up-regulation of DLEU1 was detected in breast cancer tissues and cells, particularly in tumors of higher malignancy. DLEU1 knockdown inhibited the growth and the motility of breast cancer cells. Mechanistically, DLEU1 interacted with HIF-1α to collectively activate the transcription of CKAP2. By activating ERK and STAT3 signaling, CKAP2 essentially mediated the pro-tumor activities of DLEU1. In vivo, depletion of DLEU1 inhibited xenograft growth and metastasis of breast cancer cells. Therefore, DLEU1, by acting as a coactivator for HIF-1α, up-regulates CKAP2 expression and promotes malignancy of breast cancer. Targeting DLEU1, HIF-1α, or CKAP2 may thus benefit breast cancer treatment.


Asunto(s)
Neoplasias de la Mama , Proteínas del Citoesqueleto , ARN Largo no Codificante , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Proteínas del Citoesqueleto/genética , Proteínas del Citoesqueleto/metabolismo , Femenino , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Activación Transcripcional , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo
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