The global change in protein abundance in colorectal cancer (CRC) and its contribution to tumorigenesis have not been comprehensively analyzed. In this study, we conducted a comprehensive proteomic analysis of paired tumors and adjacent tissues (AT) using high-resolution Fourier-transform mass spectrometry and a novel algorithm of quantitative pathway analysis. 12380 proteins were identified and 740 proteins that presented a 4-fold change were considered a CRC proteomic signature. A significant pattern of changes in protein abundance was uncovered which consisted of an imbalance in protein abundance of inhibitory and activating regulators in key signal pathways, a significant elevation of proteins in chromatin modification, gene expression and DNA replication and damage repair, and a decreased expression of proteins responsible for core extracellular matrix architectures. Specifically, based on the relative abundance, we identified a panel of 11 proteins to distinguish CRC from AT. The protein that showed the greatest degree of overexpression in CRC compared to AT was Dipeptidase 1 (DPEP1). Knockdown of DPEP1 in SW480 and HCT116 cells significantly increased cell apoptosis and attenuated cell proliferation and invasion. Together, our results show one of largest dataset in CRC proteomic research and provide a molecular link from genomic abnormalities to the tumor phenotype.
20 sets of indoor and outdoor size-segregated aerosol (SSA) samples (180 foils) were collected synchronously by using two 8 Stage Non-Viable Cascade Impactor from an office room in the central region of the megacity-Nanjing, China in winter and spring in 2016. The mass size distribution of SSAs was bimodal for outdoor SSAs and unimodal for indoor in both winter and spring. The crustal elements, such as K, Ca, Mg and Fe, were mainly distributed in the coarse fractions of SSAs while toxic elements such as As, Cd, Pb and Sb were enriched more in the fine fractions in both winter and spring. Moreover, indoor/outdoor (I/O) concentration ratios of SSAs and inorganic elements indicated the penetration of outdoor fine fractions of SSAs into indoor air. As, Pb, V and Mn showed higher inhalation bioaccessibility extracted by the artificial lysosomal fluid (ALF); while V, As, Sr and Cd showed higher inhalation bioaccessibility using the simulated lung fluid (SLF), suggesting differences in elemental inhalation bioaccessibility between ALF and SLF extraction. There were similar potential carcinogenic and accumulative non-carcinogenic risks via inhalation exposure to indoor and outdoor particle-bound toxic elements based on their bioaccessible concentrations. Therefore, the potential health risks to human posed by toxic elements in office rooms cannot be neglected via inhalation exposure of the fine airborne particles.
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