No abstract

Docetaxel is a first-line anticancer drug widely used in the treatment of advanced prostate cancer. However, its therapeutic efficacy is limited by its side effects and the development of chemoresistance by the tumor. Using a gene differential expression microarray, we identified 449 genes differentially expressed in docetaxel-resistant DU145 and PC3 cell lines as compared to docetaxel-sensitive controls. Moreover, western blotting and immunohistochemistry revealed altered expression of S100A4, ACKR3 and CDH1in clinical tumor samples. Cytoscape software was used to investigate the relationship between critical proteins and their signaling transduction networks. Functional and pathway enrichment analyses revealed that these signaling pathways were closely related to cellular proliferation, cell adhesion, cell migration and metastasis. In addition, ACKR3 knockout using the crispr/cas9 method andS100A4knockdownusing targeted shRNA exerted additive effects suppressing cancer cell proliferation and migration. This exploratory analysis provides information about potential candidate genes. It also provides new insight into the molecular mechanism underlying docetaxel-resistance in androgen-independent prostate cancer and highlights potential targets to improve therapeutic outcomes.

Drought stress influences the growth of plants and thus grafting has been widely used to improve tolerance to abiotic stresses. Poplars possess sex-specific responses to drought stress, but how male or female rootstock affect the grafted plant is little known. To explore the mechanisms underlying changes in drought tolerance caused by grafting, we investigated the changes in growth, leaf traits, gas exchange and antioxidant enzyme activities of reciprocally grafted seedlings between Populus euramericana cv. "Nanlin895" (NL-895) (female) and Populus deltiodes cv."3412" (NL-3412) (male) under water deficit stress with 30% field capacity for 30 d. Results showed that drought stress affected adversely growth, morphological, and physiological characteristics in all seedlings studied. Grafted seedlings with male roots can effectively alleviated the inhibition of growth induced by drought stress, as shown by higher WUE, activities of SOD, POD and CAT, and lower levels of lipid peroxidation. Male seedlings with female roots were found to be less tolerance to drought than non-grafted male clones and female scions with male roots, but more tolerance than non-grafted female clones. This results suggested that drought tolerance of grafted seedlings is primarily caused by the rootstock, although the scion also affects the grafted plant. Thus, paying attention on the root genotype can provide an important means of improving the drought tolerance of poplars.

No abstract

Background: Increasing evidence has indicated an association between differentially expressed genes (DEGs) in tumor-infiltrating immune cells (TIICs) and clinical outcome. The aim of this research is to investigate the influence of tumor microenvironment on the gene expression profile of TIICs and to identify their potential markers for modulating immune cell function in prostate cancer. Methods: In our research, CIBERSORT algorithm was utilized to calculate the proportion of the TIICs in 164 tumor and 18 control samples from The Cancer Genome Atlas cohort. The differential expression analysis was conducted using R, and then the functional and the pathway enrichments of the DEGs were analyzed using Database for Annotation, Visualization, and Integrated Discovery, followed by integrated regulatory network analysis. Results: As a result, nTreg, B cells, Th1, and DC cells were significantly increased, accompanied by largely decreased NK and NKT cells. The expressed immune-related gene correlation analysis showed that the signature gene expression extent of CD8 T cells was positively associated with CD4 memory activated T cells but negatively correlated with that of CD4 memory resting T cells. In addition, a total of 128 differentially expressed genes were identified. CytoHubba analysis obtained six hub genes, of which three prognostic-associated potential key molecules including CAV1, FLNA, and VCL were mainly involved in biological processes associated with the regulation of organic substance and synaptic connections. Conclusions: This study provides a comprehensive understanding of the landscape of TIICs and the roles of the hub genes which may be valuable markers in prostate cancer diagnosis and immunotherapy.