miR-181b functions as an oncomiR in colorectal cancer by targeting PDCD4

Programmed cell death 4 (PDCD4) is a RNA-binding protein that acts as a tumor suppressor in many cancer types, including colorectal cancer (CRC). During CRC carcinogenesis, PDCD4 protein levels remarkably decrease, but the underlying molecular mechanism for decreased PDCD4 expression is not fully understood. In this study, we performed bioinformatics analysis to identify miRNAs that potentially target PDCD4. We demonstrated miR-181b as a direct regulator of PDCD4. We further showed that activation of IL6/STAT3 signaling pathway increased miR-181b expression and consequently resulted in downregulation of PDCD4 in CRC cells. In addition, we investigated the biological effects of PDCD4 inhibition by miR-181b both in vitro and in vivo and found that miR-181b could promote cell proliferation and migration and suppress apoptosis in CRC cells and accelerate tumor growth in xenograft mice, potentially through targeting PDCD4. Taken together, this study highlights an oncomiR role for miR-181b in regulating PDCD4 in CRC and suggests that miR-181b may be a novel molecular therapeutic target for CRC.

The protective role of myeloid-derived suppressor cells in concanavalin A-induced hepatic injury

The mechanism underlying T cell-mediated fulminant hepatitis is not fully understood. In this study, we investigated whether myeloid derived suppressor cells (MDSCs) could prevent the concanavalin A (ConA)-induced hepatitis through suppressing T cell proliferation. We observed an increase in the frequencies of MDSCs in mouse spleen and liver at early stage of ConA treatment, implicating that the MDSCs might be involved in the initial resistance of mice against ConA-mediated inflammation. Subpopulation analysis showed that the MDSCs in liver of ConA-induced mice were mainly granulocytic MDSCs. Adoptive transfer of the bone marrow-derived MDSCs into ConA-treated mice showed that the MDSCs migrated into the liver and spleen where they suppressed T cell proliferation through ROS pathway. In addition, the frequencies of MDSCs in mice were also significantly increased by the treatment with immune suppressor glucocorticoids. Transfer of MDSCs into the regulatory T cell (Treg)-depleted mice showed that the protective effect of MDSCs on ConA-induced hepatitis is Treg-independent. In conclusion, our results demonstrate that MDSCs possess a direct protective role in T cell-mediated hepatitis, and increasing the frequency of MDSCs by either adoptive transfer or glucocorticoid treatment represents a potential cell-based therapeutic strategy for the acute inflammatory disease.

Chitosan inhibits high glucose-induced peroxidation and monocytes adhesion to vascular endothelial cells / 中国药理学通报

Aim To study the inhibitory effect of chitosan on peroxidation and monocytes adhesion to vascular endothelial cells induced by high concentration of glucose. Methods Human umbilical vascular endothelial cells (HUVEC) were treated with high glucose, and high glucose with different concentrations of chitosan for 24 h. Hydroxyl radicals (OH?) and malon-dialdehyde (MDA) were measured. Monocytes Raw 264.7 were pre-incubated with Rhodamin123, and then co-cultured with HUVEC for 30 min, followed bymicroscope observation and determination of the monocytes adhesion. Finally, the mRNA expression of vascular cell adhesion molecular-1 (VCAM-1) was evaluated by reverse transcription polymerase chain reaction (RT-PCR). Results Concentrations of OH? and MDA in HUVEC increased after incubation with high glucose. Both of the amount of adhesive monocytes and mRNA expression level of VCAM-1 in HUVEC were induced by high glucose. Inversely, chitosan inhibited these changes in a dose-dependent manner without any cytotoxicity to cells. Conclusion Chitosan can scavenge free radicals and prevent peroxidative injury on vascular endothelial cells, which further down-regulates the expression of VCAM-1 and consequently inhibits the adhesion of monocytes to endothlial cells.