Differential Expression Profiles and Function Prediction of tRNA-Derived Fragments in Fibrous Dysplasia

Abstract Background: Fibrous dysplasia (FD) is a benign bone disease which normal bone matrix is replaced by fibrous tissue and immature bone tissue. Transfer RNA (tRNA)-derived RNA fragments (tRFs) and tRNA halves (tiRNAs) are a type of small non-coding RNA in the transcriptome of eukaryotes that produced by specific shearing of mature tRNA. Here, we conducted a comparative analysis of the expression of tRFs/tiRNAs in BMSCs and FD BMSCs using a high‐throughput sequencing technique. Quantitative real‐time polymerase chain reaction (qRT-PCR) was used to validate the differential expressed tRFs/tiRNAs between two samples. Results: The results showed that tRF-34-87R8WP9I1EWJIQ [tDR‐001276] was significantly upregulated in FD BMSCs, and 3 downregulated tDRs (tRNA-derived small RNAs) (tRF-22-8EKSP1852 [tDR‐006826], tRF-18-H9R8B7D2 [tDR‐006049] and tRF-33-86V8WPMN1E8Y0E [tDR‐001271]) were also detected. Prediction of target genes and gene ontology (GO) and KEGG pathway analysis indicated that the upregulated tRF was mainly involved in regulation of immune response and osteoclast differentiation, which may be the underlying mechanism of FD pathological features. The downregulated tRFs/tiRNAs were related to calcium ion transport (tDR-006826), apoptotic signaling pathway and cell proliferation (tDR-006049) and endocrine system development (tDR-001271). The upregulated tRFs/tiRNAs was related to immune response (tDR-001276). The protein-protein interaction network analysis for predicted target genes established by the STRING database showed that PPP2R5A, ADAMTS1, PPARA, and POLR2C were the most frequently interacted proteins in target genes of tDR-006826, tDR-006049, tDR-001271 and tDR-001276, respectively. Conclusions: Our findings provided a comprehensive analysis of the expression of tRFs/tiRNAs in FD BMSCs and BMSCs. These differential expression tRFs/tiRNAs may be novel regulatory factors involved in FD BMSCs, and they could serve as potential therapeutic targets.