MicroRNA-541-3p/Rac2 signaling bridges radiation-induced lung injury and repair

Background: While radiation-induced lung injury decreases quality of life and suppresses efficacy of radiotherapy, to date, the relationship between radiation-induced lung injury and repair remains unclear. Our previous studies revealed that TNFRSF10B-RIPK1/RIPK3-MLKL signaling induces necroptosis o...

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Main Authors: Jiandong Zhang, Lei Ma, Limin He, Quanxiao Xu, Yan Ding, Lidong Wang
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-06-01
Series:Non-coding RNA Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468054025000228
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Summary:Background: While radiation-induced lung injury decreases quality of life and suppresses efficacy of radiotherapy, to date, the relationship between radiation-induced lung injury and repair remains unclear. Our previous studies revealed that TNFRSF10B-RIPK1/RIPK3-MLKL signaling induces necroptosis of alveolar epithelial cells and potentiates radiation-induced lung injury. We also found that microRNA-541-3p is differentially expressed in radiation-damaged lungs. The connection between microRNA-541-3p, TNFRSF10B signaling, and TGFβ1 signaling is also unclear. Objective: This study was performed to explore the regulatory effects of microRNA-541-3p on TNFRSF10B and TGFβ1 signaling. Methods: Mouse alveolar epithelial cells were transfected with a vector expressing microRNA-541-3p to regulate expression of target genes. Flow cytometry, polymerase chain reaction, and western blotting were used to analyze cell necroptosis, target gene expression, and target protein expression, respectively. Results: Overexpression of microRNA-541-3p positively regulated TNFRSF10B-RIPK1/RIPK3-MLKL signaling through Rac2 to induce cell necroptosis. MicroRNA-541-3p negatively regulates Rac2. MicroRNA-541-3p and Rac2 regulate the expression of Tgf-beta1 and its encoded proteins. Conclusions: The Rac2 gene synchronously regulates TNFRSF10B-RIPK1/RIPK3-MLKL and TGFβ1 signaling. MicroRNA-541-3P/Rac2 act as mediators of radiation damage and repair signaling.
ISSN:2468-0540