RESUMO
BACKGROUND: Diabetic retinopathy (DR) is a specific microvascular complication arising from diabetes, and its pathogenesis is not completely understood. tRNA-derived stress-induced RNAs (tiRNAs), a new type of small noncoding RNA generated by specific cleavage of tRNAs, has become a promising target for several diseases. However, the regulatory function of tiRNAs in DR and its detailed mechanism remain unknown. RESULTS: Here, we analyzed the tiRNA profiles of normal and DR retinal tissues. The expression level of tiRNA-Val was significantly upregulated in DR retinal tissues. Consistently, tiRNA-Val was upregulated in human retinal microvascular endothelial cells (HRMECs) under high glucose conditions. The overexpression of tiRNA-Val enhanced cell proliferation and inhibited cell apoptosis in HRMECs, but the knockdown of tiRNA-Val decreased cell proliferation and promoted cell apoptosis. Mechanistically, tiRNA-Val, derived from mature tRNA-Val with Ang cleavage, decreased Sirt1 expression level by interacting with sirt1 3'UTR, leading to the accumulation of Hif-1α, a key target for DR. In addition, subretinal injection of adeno-associated virus to knock down tiRNA-Val in DR mice ameliorated the symptoms of DR. CONCLUSION: tiRNA-Val enhance cell proliferation and inhibited cell apoptosis via Sirt1/Hif-1α pathway in HRMECs of DR retinal tissues.
Assuntos
Animais , Camundongos , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Retina/metabolismo , Retina/patologia , Células Endoteliais , Sirtuína 1/metabolismo , Neovascularização Patológica/genéticaRESUMO
Transfer RNA-derived small RNAs (tsRNAs) are an emerging class of non-coding single-stranded RNA that are derived from mature transfer RNA (tRNA) or tRNA precursors. They primarily consist of tRNA-derived RNA fragments (tRFs) and tRNA halves (tiRNAs). Studies have confirmed that tsRNAs are differentially expressed in a variety of tumors and involved in tumor processes including proliferation, invasion, and metastasis. Although the underlying mechanisms have not been fully elucidated, tsRNAs have the potential to be new biomarkers and therapeutic targets for tumors. This review provides an overview of the relationship between tsRNAs and common tumors to provide new ideas for the diagnosis, treatment, and prevention of tumors.