Identification and Functional Analysis of tRNA-Derived Small RNAs in the Lung Tissues of Patients With Idiopathic Pulmonary Arterial Hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) is a pulmonary vascular disease with a poor prognosis. Its pathogenesis remains unclear and the treatment methods are limited. The expression of tRNA-derived small RNA (tsRNA) in IPAH tissues remains unknown. tsRNA sequencing was conducted on lung tissue samples obtained from patients with IPAH and healthy controls. Differentially expressed tsRNAs were identified and their expression levels were validated using qRT-PCR. Functional enrichment analysis was performed to explore the potential biological roles of these tsRNAs. Lung tissue samples from three patients with IPAH and three control subjects were sequenced. A total of 382 differential tRFs and tsRNAs were identified (200 upregulated and 182 downregulated). Ten tsRNAs with the most significant differential expression were selected for further investigation. qRT-PCR analysis revealed that all five upregulated tsRNAs exhibited expression trends consistent with the sequencing results, whereas only two of the five downregulated tsRNAs showed consistency. Bioinformatics analysis predicted that five upregulated tsRNAs target the same gene, TENT4A; among them, tiRNA-1:35-Leu-TAG-2 was experimentally confirmed by dual-luciferase reporter assay. Analysis of GSE15197 and GSE113439 indicated that TENT4A expression was significantly lower in IPAH samples compared with that in the controls. Further research indicates that tiRNA-1:35-Leu-TAG-2 directly targets TENT4A and functions dependent on TENT4A. tsRNA dysregulation may play a potential role in the development of IPAH. TENT4A is a potential critical target in the pathogenesis and treatment of IPAH.