Expression profiles and potential roles of serum tRNA‑derived fragments in diabetic nephropathy

Chan Huang; Ling Ding; Jialing Ji; Yunyang Qiao; Zihuan Xia; Huimin Shi; Shiting Zhang; Weihua Gan; Aiqing Zhang

doi:10.3892/etm.2023.12010

Expression profiles and potential roles of serum tRNA‑derived fragments in diabetic nephropathy

Exp Ther Med. 2023 May 11;26(1):311. doi: 10.3892/etm.2023.12010. eCollection 2023 Jul.

Authors

Chan Huang¹, Ling Ding², Jialing Ji¹, Yunyang Qiao¹, Zihuan Xia³, Huimin Shi¹, Shiting Zhang², Weihua Gan¹, Aiqing Zhang²

Affiliations

¹ Department of Pediatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210003, P.R. China.
² Department of Pediatrics, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210031, P.R. China.
³ School of Pediatrics, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.

Abstract

Diabetic nephropathy (DN) is one of the most important causes of end-stage renal disease and current treatments are ineffective in preventing its progression. Transfer RNA (tRNA)-derived fragments (tRFs), which are small non-coding fragments derived from tRNA precursors or mature tRNAs, have a critical role in various human diseases. The present study aimed to investigate the expression profile and potential functions of tRFs in DN. High-throughput sequencing technology was employed to detect the differential serum levels of tRFs between DN and diabetes mellitus and to validate the reliability of the sequencing results using reverse transcription-quantitative PCR. Ultimately, six differentially expressed (DE) tRFs were identified (P<0.05; |log2fold change| ≥1), including three upregulated (tRF5-GluCTC, tRF5-AlaCGC and tRF5-ValCAC) and three downregulated tRFs (tRF5-GlyCCC, tRF3-GlyGCC and tRF3-IleAAT). Potential functions and regulatory mechanisms of these DE tRFs were further evaluated using an applied bioinformatics-based analysis. Gene ontology analysis revealed that the DE tRFs are mainly enriched in biological processes, including axon guidance, Rad51 paralog (Rad51)B-Rad51C-Rad51D-X-Ray repair cross-complementing 2 complex, nuclear factor of activated T-cells protein binding and fibroblast growth factor-activated receptor activity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that they are associated with axon guidance, neurotrophin signaling, mTOR signaling, AMPK signaling and epidermal growth factor receptor family signaling pathways. In conclusion, the present findings indicated that tRFs were DE in DN and may be involved in the regulation of DN pathology through multiple pathways, thereby providing a new perspective for the study of DN therapeutic targets.

Keywords: GO analysis; KEGG pathway enrichment analysis; diabetic nephropathy; expression profiles; tRNA-derived fragments.

Grants and funding

Funding: This work was supported by the National Natural Science Foundation of China (grant no. 81970664), the Natural Science Foundation of Jiangsu Province (grant nos. BK20191082 and BK20211385), 789 Outstanding Talent Program of SAHNMU (grant nos. 789ZYRC202080119 and 789ZYRC202090251), the National Innovation and Entrepreneurship Training Program for College Students (grant no. 202210312038Z) and the Science and Technology Development Foundation of Nanjing Medical University (grant no. NMUB2020049).