FOXM1/DEPDC1 feedback loop promotes hepatocarcinogenesis and represents promising targets for cancer therapy.

Forkhead box M1 (FOXM1) is a key regulator of mitosis and is identified as an oncogene involved in several kinds of human malignancies. However, how it induces carcinogenesis and related therapeutic approaches remains not fully understood. In this study, we aimed to identify a regulatory axis involving FOXM1 and its target gene DEP domain containing 1 (DEPDC1) and investigate their biological functions. FOXM1 bound to the promoter and transcriptionally induced DEPDC1 expression, in turn, DEPDC1 physically interacted with FOXM1, promoted its nuclear translocation, and reinforced its transcriptional activities. The FOXM1/DEPDC1 axis was indispensable for cancer cells, as evidenced by the fact that DEPDC1 rescued cell growth inhibition caused by FOXM1 knockdown, and silencing DEPDC1 efficiently attenuated tumor growth in a murine hepatocellular carcinoma model. Furthermore, strong positive associations between FOXM1/DEPDC1 axis and poor clinical outcome were observed in human hepatocellular carcinoma samples, further indicating their significance for hepatocarcinogenesis. Finally, we attempted to exploit immunotherapy approaches to target the FOXM1/DEPDC1 axis. Several HLA-A24:02-restricted T-cell epitopes targeting FOXM1 or DEPDC1 were identified through bioinformatic analysis. Then, T cell receptor (TCR)-engineered T cells targeting FOXM1262-270 or DEPDC1294-302 were successfully established and proved to efficiently eradicate tumor cells. Our findings highlight the significance of the FOXM1/DEPDC1 axis in the process of oncogenesis and indicate their potential as immunotherapy targets.

Microstructure Evolution of TB18 Alloy after Thermal Treatment and the Effect of Recrystallization Texture on Mechanical Properties.

In industrial production, the deformation inhomogeneity after metal forging affects the mechanical properties of various parts of the forgings. The question of whether the organization and mechanical properties of ß-titanium alloy can be improved by controlling the amount of forging deformation needs to be answered. Therefore, in this paper, a new sub-stable ß-Ti alloy TB 18 (Ti-5.3Cr-4.9Mo4.9V-4.3Al-0.9Nb-0.3Fe) was subjected to three different levels of deformation, as well as solid solution-aging treatments, and the variation rules of microstructure and mechanical properties were investigated. During the solid solution process, the texture evolution pattern of the TB18 alloy at low deformation (20-40%) is mainly rotational cubic texture deviated into α-fiber texture; at high deformation (60%), the main components of the deformed texture are α-fiber texture with a specific orientation of (114)<113-3>. After subsequent static recrystallization, the α-fiber texture is deviated to an α*-fiber texture, while the specific orientation (114)<113-3> can still be inherited as a major component of the recrystallized texture. The plasticity of the alloy in the normal direction (ND) after the solid solution is influenced by the existence of the <110>//ND texture, and the plasticity of the alloy in the ND direction after aging is determined by a combination of the volume fraction of the <110>//ND texture in the matrix phase and the volume fraction of [112-0]α//ND in the α phase. The results show that it is feasible to change the characteristics of the recrystallization texture of TB18 by controlling the deformation level of hot forging, thus realizing the modulation of the mechanical properties.