Ablation of the GDP-fucose transporter suppresses lung cancer cell proliferation and migration by reducing expression of PD-L1.

Fucosylation, an important post-translational modification, is closely related to the development of tumors. In the microenvironment of lung cancer, expression of PD-L1 and fucosylation is abnormally upregulated. However, the correlation between PD-L1 expression and its fucosylation in lung adenocarcinoma (LUAD) remains unclear. The GDP-fucose transporter (GFT) is a key molecule in cellular fucosylation. To explore the correlation between fucosylation and PD-L1 expression, we knocked out the GFT-encoding gene SLC35C1 in mouse Lewis lung adenocarcinoma cells and in human H1299 lung adenocarcinoma cells. Loss of SLC35C1 impaired the phosphorylation of EGFR and its downstream target ERK. Moreover, loss of SLC35C1 up-regulated the expression of ß-TrCP, a PD-L1 E3 ligase, thereby promoting the ubiquitination of PD-L1 and its subsequent degradation. The down-regulated expression of PD-L1 leads to a decline in lung cancer cell proliferation and migration. These results suggest that fucosylation partially influences LUAD tumorigenesis by regulating PD-L1 expression.

Ginsenoside Rg1 modulates intestinal microbiota and supports re-generation of immune cells in dexamethasone-treated mice.

Ginsenoside Rg1 is one of the major ginsenosides found in roots of Panax ginseng and Panax notoginseng. Ginsenoside Rg1 is known to possess various biological activities including immunity enhancement activity. However, it is not clear whether the regulation of immune function by Rg1 is related to the intestinal microbiota. In the present study, the immuno-modulatory and gut microbiota-reshaping effects of ginsenoside Rg1 were evaluated. Ginsenoside Rg1 acts as an immune-enhancing agent to increase spleen index and the number of T, B and dendritic cells in dexamethasone (Dex)-treated mice. Ginsenoside Rg1 also increased the production of sIgA and regulated the expression of interleukin 2 (IL-2), IL-4, IL-10 and IFN-γ. Meanwhile, Rg1 administration regulated the structure of intestinal microbiota. The relative abundance of mouse intestinal microbial groups, such as Alistipes, Ruminococcaceae, Lachnospiraceae, and Roseburia were increased by Rg1 administration, whereas a decrease in the potential pathogens like Helicobacteraceae, Dubosiella, Mycoplasma, Alloprevotella, Allobaculum was observed. Moreover, Rg1 metabolites of Lachnospiraceae bacterium enhanced the proliferation of CD4+ T cells and T regulatory (Treg) cells. Ginsenoside Rg1 improved the inflammatory condition of the colonic tissue and repaired the destructed mucosal barrier. This study suggested that Rg1 strengthens immunity with regulating the homeostasis of intestinal microbiota in mice.