ABSTRACT
RAF/MEK/ERK pathway is frequently activated in tumor. Therefore, this study will investigate the function of RUVBL1 (RAF-binding protein) in tongue squamous cell carcinoma (TSCC). Bioinformatics was performed to identify differentially expressed mRNAs (DE-mRNAs) in TCGA-oral squamous cell carcinoma, GSE13601, and GSE34105 datasets. A total of 672 shared DE-mRNAs were identified in three datasets, and they are regulating metastasis and angiogenesis. Patients with RUVBL1 low expression had high overall survival. Overexpressing RUVBL1 enhanced the viability, wound healing percentage, invasion, sphere formation, angiogenesis, and resistance to cisplatin and 5-fluorouracil in CAL-27 and SCC-4 cells, and the opposite results were obtained by knocking down RUVBL1. Moreover, overexpression of RUVBL1 bolstered tumor growth in vivo. Strikingly, RUVBL1 diminished the phosphorylation of CRAF Ser259, which led to activation of the MEK/ERK pathway. In conclusion, RUVBL1 contributes to the malignant biological behavior of TSCC via activating the CRAF/MEK/ERK pathway. This provides molecular mechanisms and perspectives for targeted therapy of the CRAF/MEK/ERK pathway.
ABSTRACT
In recent years, atmospheric pollution represented by fine particulate matter PM2.5 pollution has seriously threatened human health. Therefore, it is important to identify the risk level of population exposure to PM2.5. Based on PM2.5 remote sensing inversion data and population distribution, this study measured the risk level of population exposure to PM2.5 in the Guanzhong area. Furthermore, the methods of Theil-Sen Median trend analysis, Mann-Kendall test, and geo-spatial analysis were used to reveal the temporal and spatial characteristics of population exposures risk to PM2.5 in the Guanzhong area from 2000 to 2016. The results show that:â The years with heavy pollution and wide range in the Guanzhong area are 2006, 2007, and 2013, and the annual average concentration of PM2.5 exceeded 35 µg·m-3 in more than 40% of the Guanzhong area. From 2000 to 2016, the spatial distribution range of PM2.5 in the Guanzhong area continued to expand, forming a continuous belt-shaped concentrated distribution area from the center to the northeast. â¡More than 60% of the population in the Guanzhong area was exposed in the areas with annual average concentration of PM2.5 above 35 µg·m-3 from 2000 to 2016, and the population exposure risk continued to increase, especially after 2011, the range of the high-risk area expanded dramatically. â¢The pattern of population exposure risk to PM2.5 in the Guanzhong area was generally similar from 2000 to 2016. The areas with higher risk levels were mainly concentrated in the central Guanzhong area, forming a continuous belt-shaped distribution area from west to east. The areas with the highest value were distributed in the urban areas of several major cities, while the areas with the lowest value were mainly concentrated in the surrounding areas of Guanzhong.
