Since the incidence and mortality of colorectal cancer (CRC) are increasing in recent years, the research on the pathogenesis of colorectal cancer has attracted more and more attention. Here, our results confirmed that the mRNA expression level and proteins accumulation of TUFT1 were significantly increased in CRC tissues from late-stage CRC patients (III?+?IV) (p?<?0.001), indicated by qPCR and IHC assay. The TUFT1 expression was positively correlated with tumor stage by analyzing 126 specimens from CRC patients. Next, we found that up-regulation of TUFT1 enhanced the migration and invasion of LoVo cells, whereas the down-regulation of TUFT1 observably weakened the migration and invasion of SW837 cells, indicating that TUFT1 promotes the metastasis of CRC cells. In addition, TUFT1 overexpression increased the number of mammary spheres and vincristine resistance of LoVo cells by sphere formation assay and measuring the IC50 value, suggesting the TUFT1 promotes stemness and the vincristine resistance of CRC cells. Finally, we found that TUFT1 overexpression increased p-AKT in LoVo cells, while down-regulation of TUFT1 decreased the p-AKT levels in SW837 cells. Therefore, we determined that the function of TUFT1 in CRC depends on PI3K/AKT pathway. Taken together, these data demonstrated that TUFI1 facilitates metastasis, stemness, and vincristine resistance of colorectal cancer cells via activation of PI3K/AKT pathway, which might act as a promising therapeutic target for CRC.
Biochemical Genetics - As the endogenous ligand for the GH secretagogue receptor (GHSR), Ghrelin is aberrant expressed in multiple malignant carcinoma, and involved in regulating a number of... 相似文献
The rhizosheath, a layer of soil grains that adheres firmly to roots, is beneficial for plant growth and adaptation to drought environments. Switchgrass is a perennial C4 grass which can form contact rhizosheath under drought conditions. In this study, we characterized the microbiomes of four different rhizocompartments of two switchgrass ecotypes (Alamo and Kanlow) grown under drought or well-watered conditions via 16S ribosomal RNA amplicon sequencing. These four rhizocompartments, the bulk soil, rhizosheath soil, rhizoplane, and root endosphere, harbored both distinct and overlapping microbial communities. The root compartments (rhizoplane and root endosphere) displayed low-complexity communities dominated by Proteobacteria and Firmicutes. Compared to bulk soil, Cyanobacteria and Bacteroidetes were selectively enriched, while Proteobacteria and Firmicutes were selectively depleted, in rhizosheath soil. Taxa from Proteobacteria or Firmicutes were specifically selected in Alamo or Kanlow rhizosheath soil. Following drought stress, Citrobacter and Acinetobacter were further enriched in rhizosheath soil, suggesting that rhizosheath microbiome assembly is driven by drought stress. Additionally, the ecotype-specific recruitment of rhizosheath microbiome reveals their differences in drought stress responses. Collectively, these results shed light on rhizosheath microbiome recruitment in switchgrass and lay the foundation for the improvement of drought tolerance in switchgrass by regulating the rhizosheath microbiome. 相似文献
Drug repositioning can identify new therapeutic applications for existing drugs, thus mitigating high R&D costs. The Protein kinase 2 (CK2) inhibitor CX-4945 regulates human cancer cell survival and angiogenesis. Here we found that CX-4945 significantly inhibited the RANKL-induced osteoclast differentiation, but enhanced the BMP2-induced osteoblast differentiation in a cell culture model. CX-4945 inhibited the RANKL-induced activation of TRAP and NFATc1 expression accompanied with suppression of Akt phosphorylation, but, in contrast, it enhanced the BMP2-mediated ALP induction and MAPK ERK1/2 phosphorylation. CX-4945 is thus a novel drug candidate for bone-related disorders such as osteoporosis. 相似文献
Injured renal tubular epithelial cells (RTECs) have been recently thought to directly contribute to the accumulation of myofibroblasts in renal tubulointerstitial fibrosis through a process of epithelial to mesenchymal transition (EMT). However, the factors inducing RTECs to undergo EMT and the underlying mechanisms need to be further elucidated. This study aimed to determine the EMT-inducing activity of proinflammatory cytokine TNF-α and the role for complement 3 (C3) in this activity in an in vitro model of human RTECs (HK-2 cells). Wild type HK-2 cells were treated with TNF-α, IFN-γ or C3a; C3 siRNA- or control siRNA-carrying HK-2 cells were treated with TNF-α. Changes in the cell morphology and phenotype were assessed by microscopy, RT-PCR, western blotting, and immunostaining. TNF-α effectively induced HK-2 cells to express C3 and to transform into morphologically myofibroblast-like cells that lost E-cadherin (a classical epithelial cell marker) expression but acquired alpha-smooth muscle actin (α-SMA, a classical myofibroblast differentiation marker) expression. C3 siRNA robustly attenuated all the morphologic and phenotypic changes induced by TNF-α but the control siRNA showed no effect. Our preliminary observations suggest that TNF-α may induce EMT in RTECs through inducing C3 expression. 相似文献