CircRNA_103765 acts as a proinflammatory factor via sponging miR-30 family in Crohn's disease
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Published on: March 1, 2022
Yulan Ye1,2, Liping Zhang2, Tong Hu2
1Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, 215008, Jiangsu, China.
Insights
Circular RNAs (circRNAs) like hsa_circRNA_103765 are upregulated in inflammatory bowel disease (IBD). Silencing this circRNA protects against TNF-α-induced apoptosis, suggesting a therapeutic target for IBD.
Area of Science:
- Molecular Biology
- Immunology
- Gastroenterology
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in disease.
- The specific involvement of circRNAs in inflammatory bowel disease (IBD) pathogenesis is not well understood.
- Tumor Necrosis Factor-alpha (TNF-α) is a key mediator in IBD.
Purpose of the Study:
- To investigate the role of hsa_circRNA_103765 in Crohn's disease (CD), a type of IBD.
- To explore the regulatory mechanism of hsa_circRNA_103765 in TNF-α-induced apoptosis in intestinal epithelial cells.
- To assess the potential of hsa_circRNA_103765 as a therapeutic target for IBD.
Main Methods:
- Quantification of hsa_circRNA_103765 expression in peripheral blood mononuclear cells (PBMCs) from IBD patients.
- Correlation analysis of circRNA_103765 expression with TNF-α levels and response to infliximab treatment.
- In vitro experiments involving TNF-α stimulation, circRNA_103765 silencing, and apoptosis assays in human intestinal epithelial cells (IECs).
- Investigation of the molecular mechanism involving miR-30 family sponging and Delta-like ligand 4 (DLL4) regulation.
Main Results:
- hsa_circRNA_103765 expression was significantly elevated in active IBD patients' PBMCs.
- CircRNA_103765 levels positively correlated with TNF-α and decreased upon infliximab treatment.
- TNF-α upregulated circRNA_103765 expression in an apoptosis-dependent manner.
- Silencing circRNA_103765 protected IECs from TNF-α-induced apoptosis.
- hsa_circRNA_103765 functions as a molecular sponge for the miR-30 family, inhibiting DLL4 expression.
Conclusions:
- hsa_circRNA_103765 is a critical regulator in IBD pathogenesis, particularly in Crohn's disease.
- The mechanism involves circRNA_103765 sponging miR-30, leading to altered DLL4 expression and promoting apoptosis.
- Targeting hsa_circRNA_103765 represents a potential novel therapeutic strategy for IBD.
Abstract:
Increasing evidence suggests that circular RNAs (circRNAs) play critical roles in various pathophysiological activities. However, the role of circRNAs in inflammatory bowel disease (IBD) remains unclear. Here we report the potential roles of hsa_circRNA_103765 in regulating cell apoptosis induced by TNF-α in Crohn's disease (CD). We identify that CircRNA_103765 expression was significantly upregulated in peripheral blood mononuclear cells (PBMCs) of patients with active IBD. A positive correlation with TNF-α significantly enhanced circRNA_103765 expression in CD, which was significantly reversed by anti-TNF-α mAb (infliximab) treatment. In vitro experiments showed that TNF-α could induce the expression of circRNA_103765, which was cell apoptosis dependent, while silencing of circRNA_103765 could protect human intestinal epithelial cells (IECs) from TNF-α-induced apoptosis. In addition, circRNA_103765 acted as a molecular sponge to adsorb the miR-30 family and impair the negative regulation of Delta-like ligand 4 (DLL4). Collectively, CircRNA_103765 is a novel important regulator of the pathogenesis of IBD via sponging miR-30 family-mediated DLL4 expression changes. Blockade of circRNA_103765 could serve as a novel approach for the treatment of IBD patients.
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