Fu Xiuxiu, He Xingqiang, Yang Yanyan, Jiang Shaoyan, Wang Shizhong, Peng Xingang, Tang Guozhang, Zong Tingyu, Li Xiaolu, Zhang Ying, Zou Yulin, Yu Tao
Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao 266000, China.
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, People's Republic of China.
Genomics. 2021 Sep;113(5):3039-3049. doi: 10.1016/j.ygeno.2021.06.039. Epub 2021 Jun 30.
Emerging evidence suggests that majority of the transfer RNA (tRNA)-derived small RNA, including tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs), play a significant role in the molecular mechanisms underlying some human diseases. However, expression of tRFs/tiRNAs and their potential roles in aortic dissection (AD) remain unclear. This study examined the expression characteristics and explored the functional roles of tRFs/tiRNAs in AD using RNA-sequencing, bioinformatics, real-time quantitative reverse transcription polymerase chain reaction, and loss- and gain-of-function analysis. Results revealed that a total of 41 tRFs/tiRNAs were dysregulated in the AD group compared to the control group. Among them, 12 were upregulated and 29 were downregulated (fold change≥1.5 and p < 0.05). RT-qPCR results revealed that expressions of tRF-1:30-chrM.Met-CAT was significantly upregulated, while that of tRF-54:71-chrM.Trp-TCA and tRF-1:32-chrM.Cys-GCA were notably downregulated; expression patterns were consistent with the RNA sequencing data. Bioinformatic analysis showed that a variety of related pathways might be involved in the pathogenesis of AD. Functionally, tRF-1:30-chrM.Met-CAT could facilitate proliferation, migration, and phenotype switching in vascular smooth muscle cells (VSMCs), which might serve as a significant regulator in the progression of AD. In summary, the study illustrated that tRFs/tiRNAs expressed in AD tissues have potential biological functions and may act as promising biomarkers or therapeutic targets for AD.
新出现的证据表明，大多数源自转运RNA（tRNA）的小RNA，包括tRNA衍生片段（tRFs）和tRNA半体（tiRNAs），在某些人类疾病的分子机制中发挥着重要作用。然而，tRFs/tiRNAs在主动脉夹层（AD）中的表达及其潜在作用仍不清楚。本研究使用RNA测序、生物信息学、实时定量逆转录聚合酶链反应以及功能缺失和功能获得分析，研究了tRFs/tiRNAs在AD中的表达特征，并探讨了其功能作用。结果显示，与对照组相比，AD组共有41种tRFs/tiRNAs表达失调。其中，12种上调，29种下调（变化倍数≥1.5且p<0.05）。RT-qPCR结果显示，tRF-1:30-chrM.Met-CAT的表达显著上调，而tRF-54:71-chrM.Trp-TCA和tRF-1:32-chrM.Cys-GCA的表达显著下调；表达模式与RNA测序数据一致。生物信息学分析表明，多种相关途径可能参与AD的发病机制。在功能上，tRF-1:30-chrM.Met-CAT可促进血管平滑肌细胞（VSMC）的增殖、迁移和表型转换，这可能是AD进展中的一个重要调节因子。总之，该研究表明，AD组织中表达的tRFs/tiRNAs具有潜在的生物学功能，可能成为AD有前景的生物标志物或治疗靶点。
