Xu Jingyi, Qian Buyun, Wang Feng, Huang Ying, Yan Xinxin, Li Ping, Zhang Qian, Li Yuan, Sun Kangyun
Department of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou 215008, China.
Department of Central Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou 215008, China.
Diagnostics (Basel). 2023 Jun 14;13(12):2065. doi: 10.3390/diagnostics13122065.
It remains unclear whether transfer RNA-derived small RNAs (tsRNAs) play a role in pathological cardiac hypertrophy (PCH). We aimed to clarify the expression profile of tsRNAs and disclose their relationship with the clinical phenotype of PCH and the putative role.
Small RNA sequencing was performed on the plasma of PCH patients and healthy volunteers. In the larger sample size and angiotensin II (Ang II)-stimulated H9c2 cells, the data were validated by real-time qPCR. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were examined in Ang II-stimulated H9c2 cells. The potential role of tsRNAs in the pathogenesis of PCH was explored by bioinformatics analysis.
A total of 4185 differentially expressed tsRNAs were identified, of which four and five tsRNAs were observed to be significantly upregulated and downregulated, respectively. Of the five downregulated tsRNAs, four were verified to be significantly downregulated in the larger sample group, including tRF-30-3JVIJMRPFQ5D, tRF-16-R29P4PE, tRF-21-NB8PLML3E, and tRF-21-SWRYVMMV0, and the AUC values for diagnosis of concentric hypertrophy were 0.7893, 0.7825, 0.8475, and 0.8825, respectively. The four downregulated tsRNAs were negatively correlated with the left ventricular posterior wall dimensions in PCH patients (r = -0.4227; r = -0.4517; r = -0.5567; r = -0.4223). The levels of ANP and BNP, as well as cell size, were decreased in Ang II-stimulated H9c2 cells with 21-NB8PLML3E mimic transfection. Bioinformatics analysis revealed that the target genes of tRF-21-NB8PLML3E were mainly enriched in the metabolic pathway and involved in the regulation of ribosomes.
The plasma tRF-21-NB8PLML3E might be considered as a biomarker and offers early screening potential in patients with PCH.
目前尚不清楚转运RNA衍生的小RNA（tsRNAs）是否在病理性心肌肥厚（PCH）中发挥作用。我们旨在阐明tsRNAs的表达谱，并揭示它们与PCH临床表型的关系以及潜在作用。
对PCH患者和健康志愿者的血浆进行小RNA测序。在更大样本量和血管紧张素II（Ang II）刺激的H9c2细胞中，通过实时定量PCR验证数据。检测Ang II刺激的H9c2细胞中的心房利钠肽（ANP）和脑利钠肽（BNP）。通过生物信息学分析探索tsRNAs在PCH发病机制中的潜在作用。
共鉴定出4185个差异表达的tsRNAs，其中分别观察到4个和5个tsRNAs显著上调和下调。在5个下调的tsRNAs中，有4个在更大样本组中被证实显著下调，包括tRF-30-3JVIJMRPFQ5D、tRF-16-R29P4PE、tRF-21-NB8PLML3E和tRF-21-SWRYVMMV0，诊断向心性肥厚的AUC值分别为0.7893、0.7825、0.8475和0.8825。这4个下调的tsRNAs与PCH患者的左心室后壁尺寸呈负相关（r = -0.4227；r = -0.4517；r = -0.5567；r = -0.4223）。用21-NB8PLML3E模拟物转染Ang II刺激的H9c2细胞后，ANP和BNP水平以及细胞大小均降低。生物信息学分析显示，tRF-21-NB8PLML3E的靶基因主要富集在代谢途径中，并参与核糖体的调节。
血浆tRF-21-NB8PLML3E可被视为一种生物标志物，为PCH患者提供早期筛查潜力。
