Abstract
Aberrant expression of circular RNAs (circRNAs) is important in carcinogenesis, however, many differentially expressed circRNAs have not been functionally characterized. This study aimed to unveil the role of circRNA-dual specificity phosphatase 22 (circDUSP22) in pancreatic cancer (PaCa). Expression analyses of circDUSP22, miR-1178-3p and BCL2 interacting protein 3 (BNIP3) were carried out using quantitative real-time PCR (qRT-PCR) or western blotting. Cell growth was assessed by MTT, EdU and colony formation assays. Cell cycle distribution and cell apoptosis were investigated using flow cytometry assay. The assumed binding relationship between miR-1178-3p and circDUSP22 or BNIP3 was testified by dual-luciferase reporter and pull-down assays. The effect of circDUSP22 in vivo was identified by animal studies. The decreased expression of circDUSP22 was observed in PaCa samples and cells. CircDUSP22 ectopic expression in vitro blocked PaCa cell proliferation, arrested cell cycle and provoked cell apoptosis. CircDUSP22 targeted miR-1178-3p, whose expression was reinforced in PaCa. The inhibitory cell growth caused by circDUSP22 ectopic expression was reversed by miR-1178-3p enrichment. In addition, miR-1178-3p targeted BNIP3, whose expression was declined in PaCa. The inhibitory cell growth caused by circDUSP22 ectopic expression was reversed by BNIP3 knockdown. CircDUSP22 overexpression in vivo decelerated tumor growth. CircDUSP22 upregulation blocked PaCa development partly by targeting miR-1178-3p and increasing BNIP3, implying the potential implication of circDUSP22 in targeted therapy of PaCa.
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This work was supported by Study on the correlation between miRNA-10a expression and serum TNF-α and IL-6 levels in patients with inflammatory bowel disease and its value in diagnosis and disease assessment (No.MSZ19184).
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YS designed and performed the research; MS, YY, JQ analyzed the data; YS wrote the manuscript. All authors read and approved the final manuscript.
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Shi, Y., Shen, M., Yang, Y. et al. CircDUSP22 Overexpression Restrains Pancreatic Cancer Development via Modulating miR-1178-3p and Downstream BNIP3. Biochem Genet 61, 651–668 (2023). https://doi.org/10.1007/s10528-022-10275-8
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DOI: https://doi.org/10.1007/s10528-022-10275-8