Kura Branislav, Pavelkova Patricia, Kalocayova Barbora, Pobijakova Margita, Slezak Jan
Centre of Experimental Medicine, Slovak Academy of Sciences, Dubravska Cesta 9, 841 04 Bratislava, Slovakia.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, 832 32 Bratislava, Slovakia.
Curr Issues Mol Biol. 2024 Jul 6;46(7):7097-7113. doi: 10.3390/cimb46070423.
microRNAs (miRNAs) represent small RNA molecules involved in the regulation of gene expression. They are implicated in the regulation of diverse cellular processes ranging from cellular homeostasis to stress responses. Unintended irradiation of the cells and tissues, e.g., during medical uses, induces various pathological conditions, including oxidative stress. miRNAs may regulate the expression of transcription factors (e.g., nuclear factor erythroid 2 related factor 2 (Nrf2), nuclear factor kappa B (NF-κB), tumor suppressor protein p53) and other redox-sensitive genes (e.g., mitogen-activated protein kinase (MAPKs), sirtuins (SIRTs)), which trigger and modulate cellular redox signaling. During irradiation, miRNAs mainly act with reactive oxygen species (ROS) to regulate the cell fate. Depending on the pathway involved and the extent of oxidative stress, this may lead to cell survival or cell death. In the context of radiation-induced oxidative stress, miRNA-21 and miRNA-34a are among the best-studied miRNAs. miRNA-21 has been shown to directly target superoxide dismutase (SOD), or NF-κB, whereas miRNA-34a is a direct regulator of NADPH oxidase (NOX), SIRT1, or p53. Understanding the mechanisms underlying radiation-induced injury including the involvement of redox-responsive miRNAs may help to develop novel approaches for modulating the cellular response to radiation exposure.
微小RNA（miRNA）是参与基因表达调控的小RNA分子。它们参与从细胞稳态到应激反应等多种细胞过程的调控。细胞和组织的意外照射，例如在医疗用途期间，会引发各种病理状况，包括氧化应激。miRNA可能调控转录因子（如核因子红细胞2相关因子2（Nrf2）、核因子κB（NF-κB）、肿瘤抑制蛋白p53）以及其他氧化还原敏感基因（如有丝分裂原活化蛋白激酶（MAPK）、沉默调节蛋白（SIRT））的表达，这些基因触发并调节细胞氧化还原信号传导。在照射过程中，miRNA主要与活性氧（ROS）共同作用来调控细胞命运。根据所涉及的途径和氧化应激的程度，这可能导致细胞存活或细胞死亡。在辐射诱导的氧化应激背景下，miRNA-21和miRNA-34a是研究得最为深入的miRNA。已表明miRNA-21直接靶向超氧化物歧化酶（SOD）或NF-κB，而miRNA-34a是NADPH氧化酶（NOX）、SIRT1或p53的直接调节因子。了解辐射诱导损伤的潜在机制，包括氧化还原反应性miRNA的参与，可能有助于开发调节细胞对辐射暴露反应的新方法。
