RESUMEN
ABSTACT: Conventional therapies and novel molecular targeted therapies against breast cancer have gained great advances over the past two decades. However, poor prognosis and low survival rate are far from expectation for improvement, particularly in patients with triple negative breast cancer (TNBC). Here, we found that lncRNA DANCR was significantly overregulated in TNBC tissues and cell lines compared with normal breast tissues or other type of breast cancer. Knockdown of DANCR suppressed TNBC proliferation both in vitro and in vivo. Further study of underlying mechanisms demonstrated that DANCR bound with RXRA and increased its serine 49/78 phosphorylation via GSK3ß, resulting in activating PIK3CA transcription, and subsequently enhanced PI3K/AKT signaling and TNBC tumorigenesis. Taken together, Our findings identified DANCR as an pro-oncogene and uncoverd a new working pattern of lncRNA to mediate TNBC tumorigenesis, which may be a potential therapeutic target for improving treatment of TNBC.
Asunto(s)
Fosfatidilinositol 3-Quinasa Clase I/genética , Regulación Neoplásica de la Expresión Génica , Proteínas Proto-Oncogénicas c-akt/genética , ARN Largo no Codificante/genética , Receptor alfa X Retinoide/genética , Neoplasias de la Mama Triple Negativas/genética , Animales , Carcinogénesis/genética , Carcinogénesis/metabolismo , Carcinogénesis/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Femenino , Glucógeno Sintasa Quinasa 3 beta/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Ratones , Ratones Desnudos , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Largo no Codificante/antagonistas & inhibidores , ARN Largo no Codificante/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Receptor alfa X Retinoide/metabolismo , Transducción de Señal , Análisis de Supervivencia , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To explore the effects of all trans retinoic acid (ATRA) on the cell proliferation and expression alterations of beta-protein 1 (BP1) in human breast cancer cells lines of MDA-MB-468 and MCF-7. METHOD: The proliferation changes were detected by thiazolyl blue tetrazolium bromide (MTT) after the treatment of ATRA. At the dose of 10(-5) mol/L ATRA, the expression of BP1 was measured by reverse transcription-polymerase chain reaction (RT-PCR) and immunochemistry. RESULTS: After the treatment of ATRA, the proliferation of cells and the expression of BP1 decreased. Optical density ratio (ODR) of each group decreased from 0.85 ± 0.01, 0.71 ± 0.01 to 0.75 ± 0.02, 0.72 ± 0.06 at 24 h, 0.55 ± 0.01, 0.52 ± 0.05 at 48 h and 0.34 ± 0.02, 0.48 ± 0.03 at 72 h. Significant differences existed among different time groups (P < 0.01). The mean optical density (MOD) of each group decreased from 0.509 ± 0.081, 0.826 ± 0.015 to 0.509 ± 0.081, 0.826 ± 0.015 at 24 h, 0.270 ± 0.022, 0.641 ± 0.041 at 48 h and 0.145 ± 0.019 and 0.206 ± 0.179 at 72 h. Significant differences existed among different time groups (P < 0.01). CONCLUSION: ATRA can inhibit the proliferation and the expression of BP1 in breast cancer cells. And BP1 gene may become a therapeutic target for the ATRA-mediated inhibited growth of breast cancer cells.