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Prostate ; 79(1): 105-112, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30221381

RESUMEN

BACKGROUND: Macrophage polarization plays an important role in tumor microenvironment, which regulated the prognosis of prostate cancer. However, the potential role of it is still need further identification. METHODS: The M1 Macrophages were inducted using 100 ng/mL LPS and 100 ng/mL IFN-γ, the M1 Macrophages were inducted using 20 ng/mL IL-4. TAMs were obtained by culturing monocytes for 7 days in RPMI 1640 10% FBS with 50% of conditioned medium from PC-3 cells real-time PCR was performed to determine the expression of miR-148a, CCAT1, and PKCζ. Western blot was used to measure the level of PKCζ. The cytokine IL-10 was determined using ELISA. Transwell chamber was carried out to determine cell migration. Luciferase reporter assay was used to determine the relationship between miR-148a and PKCζ. RESULTS: The expression of miR-148a was highest in TAMs, while CCAT1 and PKCζ were highest in M1 Macrophages. Overexpressed miR-148a promoted the level of IL-10 and cell migration. Down-regulated CCAT1 promoted the level of IL-10 and cell migration, while this effects were abolished by co-transfection of si-CCAT1 and miR-148a inhibitor. PKCζ is the target gene of miR-148a. The effects of overexpressed miR-148a on the level of IL-10, genes expression, and cell migration were abolished by miR-148a mimic and pcDNA-PKCζ. In vivo experiments verified the effects of CCAT1 and miR-148a on tumor growth. CONCLUSION: CCAT1 knockdown promoted M2 macrophages polarization by up-regulating miR-148a, while miR-148a up-regulation promoted M2 macrophages polarization by down-regulating the expression of PKCζ.


Asunto(s)
Polaridad Celular/fisiología , Macrófagos/metabolismo , MicroARNs/biosíntesis , Neoplasias de la Próstata/metabolismo , Proteína Quinasa C/biosíntesis , ARN Largo no Codificante/biosíntesis , Animales , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Movimiento Celular/fisiología , Células Cultivadas , Femenino , Humanos , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Invasividad Neoplásica/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Proteína Quinasa C/genética , Células RAW 264.7 , ARN Largo no Codificante/genética , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
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