Endogenous hsa-circ_0007113 binds hsa-miR-515-5p to regulate senescence in human embryonic lung fibroblasts

Cellular senescence can lead to many diseases. However, the roles and regulation of circular RNAs (circRNAs) in senescence are poorly understood.

To investigate the altered expression pattern and mechanism of circRNA during cellular senescence and find potential targets to prevent senescence.

The Arraystar Human circRNA Array and bioinformatics were used to profile the differentially expressed circRNAs in human embryonic lung fibroblasts (IMR-90) between young cells and senescent cells and quantification in the clinical materials. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. The miRNA targets were predicted using TargetScan and miRanda.

A total of 113 differentially expressed circRNAs were identified, including 109 upregulated and 4 downregulated circRNAs (fold change >2 and p-value <0.05). Real-time qualitative polymerase chain reaction (qPCR) showed that the expression levels of 4 circRNA were significantly increased in senescent cells, and that of hsa_circ_0007113 was significantly decreased, consistent with the microarray. siRNA against hsa_circ_0007113 increased p21 and p53 expression levels and β-gal staining. The hsa_circ_0007113 has a binding site for miR-515-5p, which is involved in regulating the p53/p21 signaling pathway. The expression level of hsa_circ_0007113 was also decreased in aged people.

The study showed an altered circRNA expression pattern in cellular senescence, which might play important roles in senescence-related physiological processes. These findings provide a new direction for studying the molecular mechanism underlying senescence and a new possibility for the treatment of senescence by modulating circRNAs.