RESUMEN
MicroR-141-3p has been found to be downregulated in papillary thyroid carcinoma (PTC), while little is known about the cellular functions and precise signals elicited by miR-141-3p in PTC. The results of this study indicated that the expression of miR-141-3p was aberrantly down-regulated in PTC tissues and cell lines, compared with the adjacent normal tissues and normal thyroid epithelial cells. Furthermore, the miR-141-3p expression level was negatively associated with TNM stage and lymph node metastasis in PTC. Expression of miR-141-3p effectively inhibited cell growth, promoted apoptosis, and suppressed invasion in PTC cells. Meanwhile, miR-141-3p knockdown with miR-141-3p inhibitor reversed these effects. Consistent with the in vitro study, miR-141-3p also exhibited anti-neoplastic activity in vivo. Moreover, the results revealed that miR-141-3p directly recognized the 3' untranslated region (3'UTR) of Yin Yang 1 (YY1) and negatively regulated the expression of YY1 at both protein and mRNA levels. Ectopic expression of YY1 could effectively abrogate the anti-metastatic and proapoptotic effects of miR-141-3p. In summary, the findings suggested that miR-141-3p can act as a tumor suppressor in PTC and may be a potential therapeutic target for PTC treatment. Anat Rec, 302:258-268, 2019. © 2018 Wiley Periodicals, Inc.
Asunto(s)
Neoplasias Pulmonares/prevención & control , MicroARNs/genética , Cáncer Papilar Tiroideo/prevención & control , Neoplasias de la Tiroides/prevención & control , Factor de Transcripción YY1/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor , Movimiento Celular , Proliferación Celular , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/metabolismo , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , Factor de Transcripción YY1/genéticaRESUMEN
Hispidulin is a naturally occurring flavonoid isolated from a traditional Chinese medicinal herb, Saussurea involucrata. In this study, the regulating role of hispidulin on the mRNA expression level of enzymes involved in lipid metabolism was examined in vitro and in vivo. Moreover, the in vivo lipid-modulating effect of hispidulin was compared with that of fenofibrate, a classical PPARα agonist. Our results in present study demonstrated that hispidulin can directly bind to and activate PPARα as an agonist and thus modulate the downstream lipid-metabolizing genes. Moreover, hispidulin could attenuate dyslipidemia in high fat diet induced dyslipidemia rat model. Although further studies are needed, this study provided evidence for the potential use of hispidulin in dyslipidemia management.