Li Wenlin, Lan Ming, Xu Kun, Li Sainan, Wang Que, Chen Beidong, Huang Xiuqing, Dou Lin, Jia Na, Zhao Li, Wang Yuefeng, Jiao Xingyun, Man Yong, Liu Deping, Sun Liang, Zou Tong, He Qing, Li Jian, Yu Xue, Shen Tao
The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing 100730, China.
Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
Int J Med Sci. 2025 Jun 9;22(11):2839-2851. doi: 10.7150/ijms.106114. eCollection 2025.
tRNA-derived small RNAs (tsRNAs) are a newly recognized class of non-coding RNAs involved in regulating RNA processing and translational control. Pathological cardiac hypertrophy, characterized by left ventricular remodeling under chronic stress, serves as a critical precursor to severe cardiovascular pathologies including myocardial ischemia, infarction, and heart failure. Utilizing an angiotensin II (Ang II)-induced mouse cardiac hypertrophy model combined with tsRNA transcriptome profiling, we identified differentially expressed tsRNAs and investigated their functional relevance. Validation in neonatal mouse ventricular myocytes (NMVMs) revealed five upregulated tsRNAs associated with hypertrophic progression. Functional characterization showed that overexpressing tRF-Glu-CTC-013 significantly reduced cardiomyocyte hypertrophy and inhibited inflammation and fibrosis. Further luciferase reporter assays revealed that tRF-Glu-CTC-013 could bind to the 3' UTR of TAS1R3, thereby inhibiting its expression and enhancing the level of autophagy in NMVMs. Taken together, these findings suggest that tsRNAs may act as novel regulators of cardiac remodeling, with tRF-Glu-CTC-013 emerging as a promising therapeutic candidate for cardioprotection via anti-hypertrophic, anti-inflammatory, and anti-fibrotic mechanisms.
转运RNA衍生的小RNA（tsRNAs）是一类新发现的非编码RNA，参与调控RNA加工和翻译控制。病理性心脏肥大以慢性应激下的左心室重塑为特征，是包括心肌缺血、梗死和心力衰竭在内的严重心血管疾病的关键先兆。利用血管紧张素II（Ang II）诱导的小鼠心脏肥大模型结合tsRNA转录组分析，我们鉴定了差异表达的tsRNAs，并研究了它们的功能相关性。在新生小鼠心室肌细胞（NMVMs）中的验证揭示了与肥大进展相关的5种上调的tsRNAs。功能表征表明，过表达tRF-Glu-CTC-013可显著减轻心肌细胞肥大，并抑制炎症和纤维化。进一步的荧光素酶报告基因分析表明，tRF-Glu-CTC-013可与TAS1R3的3'UTR结合，从而抑制其表达并提高NMVMs中的自噬水平。综上所述，这些发现表明tsRNAs可能作为心脏重塑的新型调节因子，其中tRF-Glu-CTC-013通过抗肥大、抗炎和抗纤维化机制成为一种有前景的心脏保护治疗候选物。
