Pancreatic cancer is one of the most aggressive malignancies with poor prognosis and high mortality.Recent studies showed that microRNAs are dysregulated and involved in the initiation and progression of pancreatic ca...Pancreatic cancer is one of the most aggressive malignancies with poor prognosis and high mortality.Recent studies showed that microRNAs are dysregulated and involved in the initiation and progression of pancreatic cancer.In this study,we found that miR-708 was significantly downregulated in pancreatic cancer tissues and cell lines.Lentivirus-mediated overexpression of miR-708 could significantly inhibit the proliferation and invasion,while enhanced chemosensitivity to gemcitabine in both Panc-1 and SW1990 cells.Luciferase reporter assay showed that miR-708 bound the 3’-untranslated region of survivin and suppressed the expression of survivin in pancreatic cancer cells.In pancreatic cancer tissues,survivin protein was highly expressed and negatively correlated with miR-708 expression.Furthermore,the restoration of survivin expression could partially antagonize proliferation inhibition and apoptosis induction by miR-708 in pancreatic cancer cells.The Panc-1 cells with overexpression of miR-708 also showed decreased proliferation capability in nude mouse model compared with parental cells.In conclusion,our results suggest that miR-708 inhibits pancreatic cancer and could be a novel potential candidate to treat pancreatic cancer.展开更多
Autoimmune diseases are characterized by an imbalance between regulatory T cells and effector T-cell subsets, such as Thl and Th17 cells. Studies have confirmed that natural CD4＋Foxp3＋ Tregs were unstable and dysfun...Autoimmune diseases are characterized by an imbalance between regulatory T cells and effector T-cell subsets, such as Thl and Th17 cells. Studies have confirmed that natural CD4＋Foxp3＋ Tregs were unstable and dysfunctional in the presence of pro-inflammatory cytokines. In the current study, human CD39hi Tregs and CD39low Tregs were sorted from Tregs in vitro after 7 days of expansion. The functions of both Treg subsets were investigated under inflammatory conditions in vitro and in vivo. In the presence of IL-1β and IL-6, cultured CD4＋CD39hi Tregs maintained stable forkhead box protein 3 expression, whereas CD4＋CD39low Tregs lost Foxp3 expression and trans-differentiated into Thl or Th17 cells. Decreased IL-1βR and IL-6R expression on the CD39hi Tregs was the primary mechanism responsible for Treg stability. In addition, reduced activation of downstream molecules, such as STAT1 and STAT3, through the modulation of CpG demethylation played an important role. Finally, human CD4＋CD39hi Tregs but not CD4＋CD39low Tregs protected against xenograft versus host disease in model mice. These results strongly implied the physiological importance of CD39 expression and suggested that manipulation of CD39hi Tregs might represent a novel strategy for the treatment of autoimmune diseases.展开更多
基金the major science and technology project of health and family planning commission of Changzhou City(Nos.ZD201502,ZD201709).
文摘Pancreatic cancer is one of the most aggressive malignancies with poor prognosis and high mortality.Recent studies showed that microRNAs are dysregulated and involved in the initiation and progression of pancreatic cancer.In this study,we found that miR-708 was significantly downregulated in pancreatic cancer tissues and cell lines.Lentivirus-mediated overexpression of miR-708 could significantly inhibit the proliferation and invasion,while enhanced chemosensitivity to gemcitabine in both Panc-1 and SW1990 cells.Luciferase reporter assay showed that miR-708 bound the 3’-untranslated region of survivin and suppressed the expression of survivin in pancreatic cancer cells.In pancreatic cancer tissues,survivin protein was highly expressed and negatively correlated with miR-708 expression.Furthermore,the restoration of survivin expression could partially antagonize proliferation inhibition and apoptosis induction by miR-708 in pancreatic cancer cells.The Panc-1 cells with overexpression of miR-708 also showed decreased proliferation capability in nude mouse model compared with parental cells.In conclusion,our results suggest that miR-708 inhibits pancreatic cancer and could be a novel potential candidate to treat pancreatic cancer.
文摘Autoimmune diseases are characterized by an imbalance between regulatory T cells and effector T-cell subsets, such as Thl and Th17 cells. Studies have confirmed that natural CD4＋Foxp3＋ Tregs were unstable and dysfunctional in the presence of pro-inflammatory cytokines. In the current study, human CD39hi Tregs and CD39low Tregs were sorted from Tregs in vitro after 7 days of expansion. The functions of both Treg subsets were investigated under inflammatory conditions in vitro and in vivo. In the presence of IL-1β and IL-6, cultured CD4＋CD39hi Tregs maintained stable forkhead box protein 3 expression, whereas CD4＋CD39low Tregs lost Foxp3 expression and trans-differentiated into Thl or Th17 cells. Decreased IL-1βR and IL-6R expression on the CD39hi Tregs was the primary mechanism responsible for Treg stability. In addition, reduced activation of downstream molecules, such as STAT1 and STAT3, through the modulation of CpG demethylation played an important role. Finally, human CD4＋CD39hi Tregs but not CD4＋CD39low Tregs protected against xenograft versus host disease in model mice. These results strongly implied the physiological importance of CD39 expression and suggested that manipulation of CD39hi Tregs might represent a novel strategy for the treatment of autoimmune diseases.
