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Nat Commun ; 11(1): 6438, 2020 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-33353933

RESUMEN

Misregulation of long non-coding RNA (lncRNA) genes has been linked to a wide variety of cancer types. Here we report on Mammary Tumor Associated RNA 25 (MaTAR25), a nuclear enriched and chromatin associated lncRNA that plays a role in mammary tumor cell proliferation, migration, and invasion, both in vitro and in vivo. MaTAR25 functions by interacting with purine rich element binding protein B (PURB), and associating with a major downstream target gene Tensin1 (Tns1) to regulate its expression in trans. The Tns1 protein product is a critical component of focal adhesions linking signaling between the extracellular matrix and the actin cytoskeleton. Knockout of MaTAR25 results in down-regulation of Tns1 leading to a reorganization of the actin cytoskeleton, and a reduction of focal adhesions and microvilli. We identify LINC01271 as the human ortholog of MaTAR25, and importantly, increased expression of LINC01271 is associated with poor patient prognosis and metastasis. Our findings demonstrate that LINC01271 represents a potential therapeutic target to alter breast cancer progression.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante/genética , Tensinas/genética , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Núcleo Celular/genética , Proliferación Celular , Supervivencia Celular/genética , Uniones Célula-Matriz , Proteínas de Unión al ADN/metabolismo , Femenino , Humanos , Neoplasias Pulmonares/secundario , Ratones , Invasividad Neoplásica , Unión Proteica , ARN Largo no Codificante/metabolismo , Tensinas/metabolismo
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