Bone Marrow Mesenchymal Stem Cells (BMSC)-Derived MicroRNA-189 Inhibits Glioma Tumorigenesis Through Suppressing Tumor Necrosis Factor-α (TNF-α)-Mediated Nuclear Factor Kappa Light Chain Enhancer of Activated B Cells (NF-κB) Signaling Pathway

This study aims at investigating the mechanism underlying bone marrow mesenchymal stem cells (BMSC) function in glioma. Glioma cells were administered with plasmids loading NF-κB siRNA, microRNA (miRNA)-189 inhibitor, or miR-189 mimics for transfection followed by analysis of miR-189 expression by RT-qPCR, cell apoptosis by flow cytometry, cell proliferation by MTT assay,invasion and migration by Transwell assay, inflammatory factors secretion by ELISA as well as proteins expression by western blot. A mouse model of glioma was established to detect the in vivo effect of BMSCs. miR-189 was lowly expressed in glioma cell lines but enriched in BMSCs. When miR-189 was silenced, cell proliferation, invasion and migration were potentiated and apoptosis was decreased, along with enhancement of N-cadherin, Vimentin, MMP-2 and and MMP-9, and decline in Bax, cleaved casepase-3 and cleaved PARP. Silencing of NF-κB reversed the effect of miR-189 inhibitor on cell progression, accompanied with reduction of inflammatory factors. BMSCs treatment effectively promoted miR-189 expression in glioma and inactivated TNF-α/NF-κB signaling, thereby suppressing tumor growth. In conclusion, miR-189 derived from BMSC inhibits glioma progression through regulation of TNF-α/NF-κB signaling pathway.

Down-Regulation of p38 Mitogen-Activated Protein Kinases/Nuclear Factor Kappa Light Chain Enhancer of Activated B Cells (p38 MAPK/NF-κB) Signaling Pathway Promotes Bone Marrow Mesenchymal Stem Cells Differentiation into Neural Stem Cells in Healing Neurodegeneration

This study intends to promote bone marrow mesenchymal stem cells (BMSCs) differentiation into neural stem cells by down-regulating p38 MAPK/NF-κB to heal neurodegeneration. 26 patients with neurodegenerative diseases were enrolled from the Department of Neurology along with recruitment of 26 other healthy controls followed by analysis of p38 MAPK/NF-κB signaling pathway expression by ELISA. BMSCs were cultured and characterized by flow cytometry. Western blot and qRTPCR measured the p38 MAPK/NF-κB expression in the absence or presence of p38 MAPK/NF-κB inhibitors. p38 MAPK/NF-κB expression in 26 neurodegenerative patients was significantly higher than that of 26 healthy controls. The qRT-PCR and western blot results showed that the neural stem cell-specific proteins expression was increased as days went; after addition of p38 MAPK/NF-κB inhibitor, the expression of related specific genes were significantly decreased. In conclusion, inhibition of the expression of p38 MAPK/NF-κB signaling pathway can heal neurodegeneration by promoting the differentiation of BMSCs into neural stem cells.

Effect of miR-206 Derived from Bone Marrow Mesenchymal Stem Cells (BMSCs) on CD8 Expression in Gastric Cancer

The BMSCs are one of the components of tumor micro-environment and participate in tumor evolution. Our study aimed to discuss the effect of exosome derived from BMSC on gastric cancer cells. Tumor and para-tumor tissues were isolated to measure miR-206 level by RT-PCR. Gastric cancer cell behaviors were analyzed using MTT assay and scratch test. Gastric cancer model was established and treated TIGIT inhibitor to assess its role in the tumor growth in vivo. The miR-206 in exosome from BMSCs in cancer tissue was detected. CD8 expression excreted by DC could be induced after miR-206 treatment possibly through regulating the signaling pathway of TIGIT/PVR. Inhibition of TIGIT decreased tumor growth, development and reversed tumor phenotype. In conclusion, miR-206 derived from BMSCs induces CD8 expression in gastric cancer through regulating the signaling pathway of TIGIT/PVR, indicating that it might be a novel target for the treatment of gastric cancer.