No abstract

No abstract

BackgroundTo examine the influence of HOXD10 on the metabolism and growth of colon carcinoma cells by suppressing the RHOC/AKT/MAPK pathway.MethodsThirty-seven paired colon cancer and its adjacent samples from The Cancer Genome Atlas (TCGA) were analyzed. Chip Analysis Methylation Pipeline (ChAMP) analysis was employed for differential methylated points (DMPs) and the differential methylation regions (DMRs) screening. The HOXD10 mRNA expression and DNA methylation levels were detected by RT-PCR. The Cell proliferation, migration, invasion and apoptosis were respectively measured by MTT assay, transwell assay, wound healing assay and flow cytometry assay in carcinoma cell lines after treated with 5-aza-2′-deoxycytidine (5-Aza-dC) or transfected with HOXD10-expressing plasmid. The expression of HOXD10 and RHOC was revealed by immunohistochemistry in disparate differentiation colon carcinoma tissues, and the dephosphorylation of AKT and MAPK pathways were detected by RT-PCR and western blot.ResultsThe bioinformatics analysis demonstrated that HOXD10 was hypermethylated and low-expressed in colorectal cancer tissues. The detection of RT-PCR indicated the similar results in colorectal cancer cell lines and tissues. The induction of demethylation was recovered by treatment with 5-Aza-dC and the HOXD10 in colorectal cancer cell lines was re-expressed by transfection with a HOXD10 expression vector. The demethylation or overexpression of HOXD10 suppressed proliferation, migration, invasion and promoted apoptosis in colorectal cancer cells. HXOD10 suppressed the tumor growth and detected an opposite trend of protein RHOC. AKT and MAPK pathways were notably inactivated after the dephosphorylation due to the overexpression of HOXD10.ConclusionsHOXD10 was suppressed in colon adenocarcinoma cells, which down-regulated RHOC/AKT/MAPK pathway to enhance colon cancer cells apoptosis and constrain the proliferation, migration and invasion.

Both clinical and post mortem studies indicate that, in humans, the carotid sinus of the carotid artery bifurcation is one of the favored sites for the genesis and development of atherosclerotic lesions. Hemodynamic factors have been suggested to be important in atherogenesis. To understand the correlation between atherogenesis and fluid dynamics in the carotid sinus, the blood flow in artery was simulated numerically. In those studies, the property of blood was treated as an incompressible, Newtonian fluid. In fact, however, the blood is a complicated non-Newtonian fluid with shear thinning and viscoelastic properties, especially when the shear rate is low. A variety of non-Newtonian models have been applied in the numerical studies. Among them, the Casson equation was widely used. However, the Casson equation agrees well only when the shear rate is less than 10 s −1 . The flow field of the carotid bifurcation usually covers a wide range of shear rate. We therefore believe that it may not be sufficient to describe the property of blood only using the Casson equation in the whole flow field of the carotid bifurcation. In the present study, three different blood constitutive models, namely, the Newtonian, the Casson and the hybrid fluid constitutive models were used in the flow simulation of the human carotid bifurcation. The results were compared among the three models. The results showed that the Newtonian model and the hybrid model had very This project was supported by the similar distributions of the axial velocity, secondary flow and wall shear stress, but the Casson model resulted in significant differences in these distributions from the other two models. This study suggests that it is not appropriate to only use the Casson equation to simulate the whole flow field of the carotid bifurcation, and on the other hand, Newtonian fluid is a good approximation to blood for flow simulations in the carotid artery bifurcation.