B7-H3 plays an important role in tumor biology, but the molecular mechanism underlying the role of B7-H3 in tumor metastasis remains unclear. Here, our analysis of the TCGA database suggested that B7-H3 expression is associated with poor prognosis of patients with clear cell renal cell carcinoma (ccRCC). B7-H3 knockdown affected the expression of metastasis-related genes and significantly suppressed the metastasis of ccRCC cells, but had no significant effect on the proliferation of ccRCC cells. Database analysis revealed a strong positive correlation between B7-H3 and Fibronectin (FN) in ccRCC cells, and further study also confirmed that FN interacts with B7-H3. Silencing FN expression inhibited the migration and invasion of ccRCC cells, whereas exogenous FN promoted the

Anti-apoptosis has been widely accepted as a hallmark of malignancy. B7-H3, a type I transmembrane protein, plays a key role in anti-apoptosis and immune escape, but its regulation during cancer development remains unclear. To investigate how the effect of anti-apoptosis is regulated by B7-H3 in gastric cancer, we stably knocked down B7-H3 gene by shRNA in MGC-803 and MKN-45 cells. The correlation between B7-H3 and Fibronectin (FN) expression were investigated by bioinformatics in public data from TCGA (The Cancer Genome Atlas). Here, we reported that B7-H3 expression is positively correlated with FN in clinical gastric cancer samples, and B7-H3 promoted adhesion and inhibited apoptosis of gastric cancer cell through an FN-dependent pathway. Mechanistically, B7-H3 interacted with FN and subsequently activated PI3K/AKT signaling pathway, a critical mediator of oncogenic signaling. In addition, exogenous FN could inhibit the expression of pro-apoptosis-related proteins such as Caspase 3, Caspase 8, Caspase 9, Bax , p53, Apaf-1 and Cleaved PARP, and upregulated the levels of signal molecule p-PI3K, p-AKT and anti-apoptotic proteins Bcl-2 in B7-H3 high group, as compared with those in B7-H3 low group. In conclusion, we here for the first time revealed that B7-H3 inhibits apoptosis of gastric cancer cell through regulation of FN-mediated PI3K/AKT signaling pathways.

Background: Interleukin 1 beta (IL-1β) is considered to be a mediator of infectious, inflammatory and autoimmune diseases, and the kinetics of its production is relevant to understanding the pathogenesis of these diseases. Lysophosphatidic acid (LPA), the structurally simplest bioactive phospholipid, is necessary for homeostasis in various physiological and pathophysiological processes and plays a pivotal role in wound healing. Skin trauma can not only weaken the barrier function, but also cause pain and infection. Chronic wounds are characterized by impaired healing and uncontrolled inflammation that damages the protection of the immune system. The aim of this study is to investigate whether inflammatory factor IL-1β has an effect on LPA in the wound healing model. Results: In this study, the kinetics of IL-1β gene expression was studied in vivo and in vitro with a wound healing model by quantitative real-time polymerase chain reaction (qRT-PCR) through LPA treatment. As a result, we found that LPA up-regulated inflammatory factor IL-1β in HaCaT cell and skin wound healing. The pro-inflammatory cytokines IL-1β mRNA had higher expression in LPA-treated mice group 3 days after the treatment. In vitro, after the treatment with LPA (20 μM) for 6, 12, and 24 hours, IL-1β mRNA expression increased by 61.16%, 129.39%, and 117.07%, respectively. Conclusion: These results strongly suggest that IL-1β may regulate LPA-accelerated skin wound healing. IL-1β has significant efficacy, and our observations are of interest to the development of drugs targeting LPA in skin therapy.