Mxi1 participates in the progression of lung cancer via the microRNA-300/KLF9/GADD34 Axis.

The purpose of the current study was to define the role of MAX interactor 1 (Mxi1) in the pathogenesis of lung cancer and its underlying molecular mechanism. Bioinformatics analysis was performed to identify important regulatory pathway related to lung cancer. Dual luciferase reporter and ChIP assays were adopted to validate the interaction among Mxi1, miR-300 and KLF9. Loss- and gain-of-function studies were conducted to determine the roles of Mxi1, miR-300, and KLF9 in cell proliferation, migration, and invasion in vitro and their effects on myeloid-derived suppressor cell (MDSC) recruitment in vivo. Mxi1 was poorly expressed in lung cancer tissues and cells and its poor expression was associated with poor prognosis. Mxi1 inhibited miR-300 by suppressing its transcription. miR-300 suppressed the expression of KLF9, and KLF9 negatively regulated GADD34 expression in lung cancer cells. Mxi1 or KLF9 elevation or miR-300 repression inhibited lung cancer cell proliferation, as evidenced by reduced Ki67 and PCNA expression, and lowered invasion and migration. In vivo findings revealed that silencing KLF9 induced tumor growth by enhancing MDSC-mediated immunosuppression through upregulation of GADD34. Collectively, these findings suggest that Mxi1 can inhibit lung cancer progression by regulating the miR-300/KLF9 axis and GADD34-mediated immunosuppression.

The effects of TGF-ß1 on staphylococcus epidermidis biofilm formation in a tree shrew biomaterial-centered infection model.

BACKGROUND: Transforming growth factor-ß1 (TGF-ß1) has a wide range of biological functions. It antagonizes lymphocyte response, inhibits pro-inflammatory cytokines, and serves as a signal to turn off the immune response and inflammatory response. To study the correlation between TGF-ß1 and T helper (Th)1/Th2 cytokine levels in tree shrews, and to explore the effects of different levels of TGF-ß1 on central venous catheter (CVC)-centered Staphylococcus epidermidis biofilm formation in tree shrews. METHODS: Tree shrews were injected with different concentrations of TGF-ß1, and venous blood was drawn after 48 h to measure the levels of Th1 and Th2 cytokines. A CVC was placed into the femoral vein, and TGF-ß1 at different concentrations and PIA- (ATCC12228) and PIA+ (ATCC35984) standard strains of Staphylococcus epidermidis were injected into the tree shrews to establish a biomaterial-centered infection (BCI) model. After 72 h, the CVC was removed, and biofilm formation was detected using the API bacterial identification system, semi-quantitative biofilm formation assay, and scanning electron microscopy. RESULTS: In the groups treated with TGF-ß1 at different concentrations, the levels of Th1 cytokines interleukin-2 (IL-2), tumor necrosis factor (TNF), and interferon-γ (IFN-γ) were lower than those of normal group, while the levels of Th2 cytokines IL-6, IL-4 and IL-10 were higher than those of normal group. In the TGF-ß1 groups at different concentrations, the positive rate of Staphylococcus epidermidis ATCC35984 biofilm formation was higher than that in non-TGF-ß1 group, while there was no significant difference in the positive rate of Staphylococcus epidermidis ATCC12228 biofilm formation compared with that of the non-TGF-ß1 group. CONCLUSIONS: TGF-ß1 causes the imbalance of Th1/Th2 cytokines and Th1/Th2 shift in tree shrews, leading to Th1 cell-led decline in cellular immune function. TGF-ß1 promotes PIA+ Staphylococcus epidermidis biofilm formation in the tree shrew BCI model, but it has no significant influence on PIA-Staphylococcus epidermidis biofilm formation on the surface of CVCs.