The Role Of MicroRNA-155 In Glioma And Its Mechanism

[Background]Glioma is the most common intracranial malignancy.Surgical treatment and active chemoradiotherapy,the tumor recurrence rate is still very high。Adoptive immune therapy has been proved to be a promising strategy for glioma treatment.The theoretical basis of tumor immunotherapy is that the immune system has the ability to recognize tumor-associated antigens and regulate the body’s immune system to attack tumor cells.[Objective]A lot of mammalian micro-RNAs have been identified in regulating immune system function.In our study,we tried to investigate the role of microRNA-155 in promoting its anti-glioma ability and potential mechanism.[Methods]1.we generated microRNA-155 knock out mouse model and glioma mouse model.Then the progression of glioma and the accumulation of CD8⁺T cells were compared between WT and miR-155^-/-mice.2.T cells were transfected with miR-155 mimics and inhibitors for proliferative and invasive activity analysis.3.we evaluated the Akt and Stat5 signaling and the expression level of FoxO3a.4.we determined the regulatory ability of FoxO3a to Akt and Stat5 signaling by changing the expression level of FoxO3a in T cells.[Results]1.We found that increased progression of glioma in MicroRNA-155deficiency mice with the reduced accumulation of CD8+T cells in glioma.2.The proliferative and invasive ability of T cells was regulated by MicroRNA-155.3.MicroRNA-155 could induce the activation of Akt and Stat5 signaling by inhibiting its target gene FoxO3a.4.FoxO3a was the negative regulator of Akt and Stat5 signaling.[Conclusions]MicroRNA-155 deficiency in CD8⁺T cells inhibit its anti-tumor activity by inhibiting the proliferative and invasive activity of T cells.Besides,MicroRNA-155 regulating the function of T cells by inhibiting the expression of FoxO3a which was a negative regulator of Akt and Stat5 signaling.These findings in our study might be a new strategy for the immuno-therapy of glioma.