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

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research Pub Date : 2025-01-27 DOI:10.1016/j.ncrna.2025.01.010

Jiandong Zhang , Lei Ma , Limin He , Quanxiao Xu , Yan Ding , Lidong Wang

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引用次数: 0

Abstract

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.

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MicroRNA-541-3p/Rac2信号在辐射诱导的肺损伤和修复中起桥梁作用

虽然放射性肺损伤会降低患者的生活质量并抑制放射治疗的疗效，但迄今为止，放射性肺损伤与修复之间的关系尚不清楚。我们之前的研究表明，TNFRSF10B-RIPK1/RIPK3-MLKL信号可诱导肺泡上皮细胞坏死，并增强辐射诱导的肺损伤。我们还发现microRNA-541-3p在辐射损伤的肺中有差异表达。microRNA-541-3p、TNFRSF10B信号和tgf - β1信号之间的联系也不清楚。目的探讨microRNA-541-3p对TNFRSF10B和tgf - β1信号通路的调控作用。方法用表达microRNA-541-3p的载体转染小鼠肺泡上皮细胞，调控靶基因的表达。流式细胞术、聚合酶链反应和western blotting分别检测细胞坏死、靶基因表达和靶蛋白表达。结果microRNA-541-3p过表达通过Rac2正向调节TNFRSF10B-RIPK1/RIPK3-MLKL信号通路，诱导细胞坏死。MicroRNA-541-3p负调控Rac2。MicroRNA-541-3p和Rac2调节tgf - β 1及其编码蛋白的表达。结论Rac2基因同步调控TNFRSF10B-RIPK1/RIPK3-MLKL和tgf - β1信号通路。MicroRNA-541-3P/Rac2作为辐射损伤和修复信号的介质。

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来源期刊

Non-coding RNA Research Medicine-Biochemistry (medical)

CiteScore

7.70

自引率

6.00%

发文量

审稿时长

49 days

期刊介绍： Non-coding RNA Research aims to publish high quality research and review articles on the mechanistic role of non-coding RNAs in all human diseases. This interdisciplinary journal will welcome research dealing with all aspects of non-coding RNAs-their biogenesis, regulation and role in disease progression. The focus of this journal will be to publish translational studies as well as well-designed basic studies with translational and clinical implications. The non-coding RNAs of particular interest will be microRNAs (miRNAs), small interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), U-RNAs/small nuclear RNAs (snRNAs), exosomal/extracellular RNAs (exRNAs), Piwi-interacting RNAs (piRNAs) and long non-coding RNAs. Topics of interest will include, but not limited to: -Regulation of non-coding RNAs -Targets and regulatory functions of non-coding RNAs -Epigenetics and non-coding RNAs -Biological functions of non-coding RNAs -Non-coding RNAs as biomarkers -Non-coding RNA-based therapeutics -Prognostic value of non-coding RNAs -Pharmacological studies involving non-coding RNAs -Population based and epidemiological studies -Gene expression / proteomics / computational / pathway analysis-based studies on non-coding RNAs with functional validation -Novel strategies to manipulate non-coding RNAs expression and function -Clinical studies on evaluation of non-coding RNAs The journal will strive to disseminate cutting edge research, showcasing the ever-evolving importance of non-coding RNAs in modern day research and medicine.