RESUMEN
Tumor metastasis is a leading cause of death in nasopharyngeal carcinoma (NPC) patients. Previous research has identified that transcription factor Yin Yang 1 (YY1) acts as a tumor suppressor that inhibits cell proliferation and tumor growth in NPC; however, the role and the molecular mechanisms of YY1 in NPC invasion and metastasis remain unclear. In this study, we discovered that YY1 could inhibit the migration and invasion of NPC cells in vitro as well as NPC xenograft tumor metastasis in vivo. Furthermore, we identified eIF4E as a direct downstream target of YY1, and YY1 could negatively regulate the expression of eIF4E at transcriptional level. Moreover, we found that eIF4E promoted the migration and invasion of NPC cells as well as NPC lung metastasis, suggesting its potential as a pro-metastatic mediator in NPC. Importantly, restoring eIF4E expression could partially reverse the inhibitory effects of YY1 on NPC malignancy. In consistent with these findings, the expression of YY1 was downregulated while eIF4E was upregulated in NPC patients with metastasis, and there was a negative correlation between YY1 and eIF4E expression. Collectively, our results indicate that YY1 suppresses the invasion and metastasis of NPC by negatively regulating eIF4E transcription. Therefore, targeting the YY1/eIF4E transcriptional axis could be a potential therapeutic strategy for the treatment of patients with NPC.
RESUMEN
Yin-Yang 1 (YY1) is a member of the GLI-Kruppel family of zinc finger proteins and plays a vital dual biological role in cancer as an oncogene or a tumor suppressor during tumorigenesis and tumor progression. The tumor microenvironment (TME) is identified as the "soil" of tumor that has a critical role in both tumor growth and metastasis. Many studies have found that YY1 is closely related to the remodeling and regulation of the TME. Herein, we reviewed the expression pattern of YY1 in tumors and summarized the function and mechanism of YY1 in regulating tumor angiogenesis, immune and metabolism. In addition, we discussed the potential value of YY1 in tumor diagnosis and treatment and provided a novel molecular strategy for the clinical diagnosis and treatment of tumors.
RESUMEN
This study aimed to investigate the antihyperlipidemic and anti-inflammatory effect of zingiberene (ZBN) on isoproterenol-(ISO) induced myocardial infarction in rats. ZBN (10 mg/kg b.wt.) was orally administered to rats for 21 days and ISO (85 mg/kg b.wt.) was subcutaneously injected into the rats at 24 h intervals for the last 2 consecutive days. We observed increased serum creatine kinase, creatine kinase-MB, cardiac troponin T, and I levels in ISO-treated MI rats. Conversely, ZBN oral administration significantly prevented in cardiac marker enzyme activities in ISO-mediated rats. We also noticed that ZBN oral administration prevented ISO-induced expression of lipid peroxidative markers, total cholesterol, triglycerides, phospholipids, free fatty acids, very-low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C) to the normal basal level. Furthermore, ZBN restored ISO-mediated antioxidant status, increased level of high-density lipoprotein cholesterol (HDL-C), and tissue phospholipids to the near-normal levels. Besides, ZBN pre-treatment significantly reduced the level of inflammatory markers (TNF-α, IL-6, NF-κB, and IL-1ß) in ISO-induced MI in rats. We noticed that ZBN pretreatment inhibited the pro-apoptotic proteins Bax and cytochrome c and increased the Bcl-2 expression in ISO induced rats. The gene expression profiling by qRT-PCR array illustrates that ZBN treatment prevents the ISO mediated activation of cardiac markers, inflammatory, and fibrosis-related genes in the heart tissue. Taken together, pre-treatment with ZBN attenuated ISO-induced MI resolved exhibits the anti-inflammatory and antiapoptotic effect.