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MicroRNA-155 deficiency in CD8+ T cells inhibits its anti-glioma immunity by regulating FoxO3a
1Department of Neurosurgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. 352430864@qq.com.
Objective:
A lot of mammalian micro-RNAs have been identified in regulating immune system function. Here, the aim of this study was to investigate the role of microRNA-155 in promoting anti-glioma ability and its potential mechanism.
Materials And Methods:
In this study, we constructed microRNA-155 knockout mouse model and glioma mouse model. Subsequently, the progression of glioma and the accumulation of CD8+ T cells were compared between WT and miR-155-/- mice. T cells were transfected with miR-155 mimics and inhibitors, and the proliferative and invasive activities were analyzed. At the same time, we evaluated Akt and Stat5 signaling transduction and the expression level of FoxO3a. Finally, the regulatory ability of FoxO3a to Akt and Stat5 signaling was determined by changing the expression level of FoxO3a in T cells.
Results:
We found significantly increased progression of glioma in MicroRNA-155 deficiency mice with reduced accumulation of CD8+ T cells in glioma. The proliferative and invasive abilities of T cells were regulated by MicroRNA-155. Besides, microRNA-155 could induce the activation of Akt and Stat5 signaling by inhibiting its target gene FoxO3a. Furthermore, FoxO3a was a negative regulator of Akt and Stat5 signaling.
Conclusions:
MicroRNA-155 deficiency in CD8+ T cells inhibited anti-tumor activity by suppressing the proliferative and invasive activities of T cells. FoxO3a was a negative regulator of Akt and Stat5 signaling. Besides, microRNA-155 regulated the function of T cells by inhibiting the expression of FoxO3a. Our findings might be a new strategy for the immunotherapy of glioma.
Insights
MicroRNA-155 enhances anti-glioma immunity by boosting CD8+ T cell function. Its deficiency impairs T cell activity and promotes glioma progression, highlighting a potential immunotherapy target.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- MicroRNAs (miRNAs) are key regulators of immune responses.
- The role of specific miRNAs, like microRNA-155 (miR-155), in glioma immunity requires further elucidation.
Purpose of the Study:
- To investigate the function of miR-155 in promoting anti-glioma immunity.
- To elucidate the underlying molecular mechanisms of miR-155's action in T cells.
Main Methods:
- Generation of miR-155 knockout and glioma mouse models.
- Analysis of glioma progression and CD8+ T cell infiltration.
- In vitro studies on T cell proliferation and invasion upon miR-155 modulation.
- Evaluation of Akt, Stat5, and FoxO3a signaling pathways.
Main Results:
- miR-155 deficiency led to increased glioma progression and decreased CD8+ T cell accumulation.
- miR-155 positively regulated T cell proliferation and invasion.
- miR-155 inhibited FoxO3a expression, activating Akt and Stat5 signaling.
Conclusions:
- miR-155 is crucial for anti-glioma T cell activity.
- The miR-155/FoxO3a axis regulates T cell function and anti-tumor immunity.
- Targeting miR-155 presents a potential novel strategy for glioma immunotherapy.
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