The circular RNA expression profile of human auricle cartilage and the role of circCOL1A2 in isolated microtia.

ABSTRACT

Microtia is one of the most common craniofacial birth defects worldwide, and its primary clinical manifestation is auricle deformity. Epigenetic factors are known to contribute to the etiology of microtia, yet the involvement of circular RNAs (circRNAs) in human auricle development and their association with microtia remains poorly understood. In this study, we aimed to analyze differentially expressed circRNAs and explore their functional implications in isolated microtia. By employing circRNA microarray analysis and bioinformatics approaches, we identified 340 differentially expressed circRNAs in auricle cartilage of patients with isolated microtia, comprising 152 upregulated and 188 downregulated circRNAs. A circRNA-mRNA co-expression network was constructed, followed by gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Subsequently, we selected four significantly upregulated circRNAs from the co-expression network based on their association with cartilage development and validated their expressions in 30 isolated microtia and 30 control clinical auricle cartilage samples. Among these circRNAs, circCOL1A2, the most significantly upregulated circRNA, was selected as a representative circRNA for investigating its role in isolated microtia. Overexpression of circCOL1A2 significantly inhibited chondrocyte proliferation and chondrogenic differentiation of human mesenchymal stem cells. Additionally, circCOL1A2 upregulated Dermatan Sulfate Epimerase Like (DSEL) expression by sponging miR-637 through the competing endogenous RNA (ceRNA) mechanism. Notably, the downregulation of DSEL attenuated the inhibitory effect of circCOL1A2 overexpression on cell proliferation and chondrogenic differentiation. Collectively, these findings highlight the involvement of circCOL1A2 in the pathogenesis of isolated microtia and emphasize the potential significance of dysregulated circRNAs in disease development.