Zakharova Irina O, Bayunova Liubov V, Avrova Natalia F
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Thorez av. 44, 194223 St. Petersburg, Russia.
Curr Issues Mol Biol. 2025 Jun 17;47(6):462. doi: 10.3390/cimb47060462.
In recent years, it has become clear that non-coding RNAs play an important role in regulating the development of various organs and pathological conditions, including cerebral ischemia and reperfusion. Non-coding RNAs are mainly represented by long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs). Most of the human genome is transcribed into such RNAs. Excessive activation of autophagy during cerebral ischemia and reperfusion results in autophagic neuronal death in addition to apoptotic death. This review shows that regulation occurs via the lncRNA (or circRNA)/miRNA/target protein signaling axes. A knockdown or a decrease in lncRNA level can lead to a significant increase in miRNA levels, followed by a decrease in the levels of messenger RNA (mRNA) of autophagy-related protein (ATG) and ATG protein itself. This leads to inhibition of autophagy and alleviation of brain ischemia-reperfusion injury. Changes in miRNA and mRNA levels of the target protein occur due to the presence of complementary nucleotide sequences with lncRNA and miRNA, respectively. If the target protein is not an ATG protein, neuroprotection during cerebral ischemia and reperfusion can result from both inhibition and activation of autophagy. The further study of the regulatory role of non-coding RNAs is important as it may help to counteract the effects of excessive autophagy activation and other adverse effects of ischemia-reperfusion injury.
近年来，越来越明显的是，非编码RNA在调节包括脑缺血再灌注在内的各种器官发育和病理状况中发挥着重要作用。非编码RNA主要包括长链非编码RNA（lncRNA）、微小RNA（miRNA）和环状RNA（circRNA）。人类基因组的大部分转录成此类RNA。脑缺血再灌注期间自噬的过度激活除导致凋亡性死亡外，还会导致自噬性神经元死亡。本综述表明，这种调节是通过lncRNA（或circRNA）/miRNA/靶蛋白信号轴发生的。lncRNA水平的敲低或降低可导致miRNA水平显著升高，随后自噬相关蛋白（ATG）的信使RNA（mRNA）水平及ATG蛋白本身水平降低。这会导致自噬受到抑制，脑缺血再灌注损伤得到减轻。由于分别存在与lncRNA和miRNA互补的核苷酸序列，靶蛋白的miRNA和mRNA水平会发生变化。如果靶蛋白不是ATG蛋白，脑缺血再灌注期间的神经保护作用可能源于自噬的抑制和激活。对非编码RNA调节作用的进一步研究很重要，因为这可能有助于对抗自噬过度激活的影响以及缺血再灌注损伤的其他不良影响。
