Integrated Analysis of tRNA-Derived Small RNAs Reveals New Therapeutic Genes of Hyperbaric Oxygen in Diabetic Foot Ulcers

Abstract

Background: To reveal the alterations of tRNA-derived small RNA (tsRNA) expression profiles induced by hyperbaric oxygen (HBO) treatment in diabetic foot ulcers (DFUs) and investigate new therapeutic targets. Materials & methods: tsRNA sequencing was employed in normal skin tissue, in DFUs, and after HBO treatment groups. A quantitative real-time PCR was used to validate tsRNA sequencing results and their targets levels. Bioinformatics analysis was performed to reveal their therapeutic functions in DFUs. Results: A total of 22 tsRNAs were differentially expressed in the three groups. Three selected tsRNAs were validated by quantitative real-time PCR for further analysis, which were all significantly overexpressed in DFU while being normally expressed after HBO treatment. Bioinformatics analysis disclosed that these tsRNAs may play therapeutic roles through the regulation of the Wnt signaling pathway. Conclusion: tsRNAs may be novel useful targets for HBO to treat DFUs.

Tweetable abstract

tRNA-derived small RNAs (tsRNAs) are small, noncoding RNAs that play a variety of biological functions in the course of multiple diseases. This study investigated new therapeutic targets of hyperbaric oxygen treatment in diabetic foot ulcers (DFUs). A total of 22 tsRNAs were differentially expressed in normal, DFU and hyperbaric oxygen groups. The authors confirmed that three tsRNAs (tRF-Gly-CCC-006, tRF-Val-AAC-016 and tRF-Val-TAC-016) increased signifcantly in DFUs. Bioinformatics analysis showed that these tsRNAs may be beneficial in hyperbaric oxygen treatment through the regulation of the Wnt signaling pathway. In conclusion, tsRNAs may be useful targets with the therapeutic potential to treat DFUs.

Keywords::

• angiogenesis
• diabetic foot ulcer
• hyperbaric oxygen
• sequencing
• tsRNA

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2021-0284

Author contributions

Z Yan performed the experiments, analyzed the data and wrote the original draft article. H Li and Q Zhou collected samples. B Jiang and Z Luo performed RNA extraction and qPCR. Y Ran and M Duan completed the sequencing and interpreted the experiment data. X Cui and M Huang designed the experiment. Z Yan and P Zhang designed the experiments and revised the article. All authors read and approved the final manuscript. All authors have contributed to the article and were included in the author list.

Financial & competing interests disclosure

This work was supported by the National Natural Science Foundation of China (81974287, 81971820) and the Key Research and Development Project in Hunan Province (2018SK2089). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing support was provided by EditorBar (www.editorbar.com) for the English language review.

Ethical conduct of research

The study was approved and supervised by the Ethics Committees of Xiangya Hospital, Central South University. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (81974287, 81971820) and the Key Research and Development Project in Hunan Province (2018SK2089). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing support was provided by EditorBar (www.editorbar.com) for the English language review.