ABSTRACT
Background: Diabetes mellitus (DM) and complications such as chronic kidney disease and cardiovascular symptoms pose a substantial public health burden. Increasing studies have shown that circular RNAs (circRNAs) regulate many gene expressions that are essential in diverse pathological and biological procedures. However, the roles of particular circRNAs in DM are unclear.
Methods: In the current investigation, endothelial progenitor cells (EPCs) were used to search for abnormal expression of circRNAs by using high-throughput sequencing under high glucose (HG) conditions. The regulatory mechanisms and targets were then studied through bioinformatics analysis, luciferase reporter analysis, angiogenic differentiation experiments, flow cytometry detection of apoptosis and RT-qPCR analysis.
Results: The circ-Astn1 expression in EPCs decreased after HG treatment. Overexpression or circ-Astn1 suppressed HG induced endothelial cell damage. MicroRNA (miR)-138-5p and SIRT5 were found to be the downstream targets of circ-Astn1 through luciferase reporter analysis. SIRT5 downregulation or miR-138-5p overexpression reversed circ-Astn1’s protective effect against HG induced endothelial cell dysfunction, including apoptosis and abnormal vascular differentiation. Furthermore, circ-Astn1 overexpression promoted autophagy activation by increasing SIRT5 expression under HG conditions. Our findings suggest that circ-Astn1 mediated promotion of SIRT5 facilitates autophagy by sponging miR-138-5p.
Conlusion: Together, our findings show that the overexpression of circ-Astn1 suppresses HG induced endothelial cell damage by targeting miR-138-5p/SIRT5 axis.
Disclosure Statement
No potential conflict of interest was reported by the author(s).
Data Availability Statement
The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.
Author’s Contributions
YF W and MQ L contributed to the study conception and design. All authors collected the data and performed the data analysis. All authors contributed to the interpretation of the data and the completion of figures and tables. All authors contributed to the drafting of the article and final approval of the submitted version.
Ethics Approval and Consent to Participate
The present study was granted an exemption from requiring ethics approval by Tenth People’s Hospital of Tongji University because it did not involve human subjects. All patients gave their written informed consent.
List of Abbreviation
DM | = | Diabetes mellitus |
circRNAs | = | circular RNAs |
EPCs | = | endothelial progenitor cells |
Supplementary Material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/07435800.2024.2365887