hsa_circRNA_001587 upregulates SLC4A4 expression to inhibit migration, invasion, and angiogenesis of pancreatic cancer cells via binding to microRNA-223

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 319; no. 6; pp. G703 - G717
• Main Authors: Zhang, Xiutian, Tan, Peng, Zhuang, Yuan, Du, Lei
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.12.2020
• Subjects: Adult; Aged; Angiogenesis; Animals; Argonaute 2 protein; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell proliferation; Circular RNA; Female; Humans; Immunoprecipitation; Male; Matrix metalloproteinase; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Metalloproteinase; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; Neoplasm Invasiveness - genetics; Neovascularization, Pathologic - genetics; Pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Pheochromocytoma cells; Reporter gene; RNA, Circular - genetics; Sodium-Bicarbonate Symporters - biosynthesis; Sodium-Bicarbonate Symporters - genetics; Transfection; Tumorigenesis; Up-Regulation - genetics; Vascular endothelial growth factor; Xenograft Model Antitumor Assays; Xenografts; microRNA-223; pancreatic cancer; invasion; angiogenesis; migration; solute carrier family 4 member 4; hsa_circular RNA 001587
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.00118.2020

Pancreatic cancer (PC) is a malignant tumor that is difficult to diagnose and treat. Circular RNAs (circRNAs) are biomarkers that may be used to diagnose certain cancers or act as targets for cancer treatment. We aimed to explore the functions of human circular RNA 001587 (hsa_circRNA_001587) on the progression of PC and the underlying mechanism. The expression pattern of hsa_circRNA_001587 and microRNA-223 (miR-223) in PC tissues and cells was determined by RT-qPCR. Dual-luciferase reporter gene assay, RNA-pulldown, Argonaute 2 (AGO2) immunoprecipitation assay, and Northern blot analysis were applied to verify the binding relationships among hsa_circRNA_001587, miR-223 and solute carrier family 4 member 4 (SLC4A4). Further analysis of their roles was performed in PC cell line PANC-1. Moreover, we either downregulated or upregulated the expression of hsa_circRNA_001587, miR-223, and SLC4A4 by transfection in vitro. A mouse xenograft model of PC cells was established to evaluate tumor growth in vivo. hsa_circRNA_001587 was poorly expressed, but miR-223 was highly expressed in PC tissues and cell lines. Upregulation of hsa_circRNA_001587 downregulated the expression of matrix metalloproteinase-2 and-9, minichromosome maintenance 2, and vascular endothelial growth factor, and decreased the proliferation, migration, invasion, angiogenic and tumorigenic abilities of PC cells. MiR-223, which can bind with hsa_circRNA_001587, reversed the effects of hsa_circRNA_001587 on PC cells. In addition, SLC4A4 was identified as a target of miR-223, and its knockdown could counteract the regulatory effects of overexpressed hsa_circRNA_001587 or inhibited miR-223 expression on PC cells. Therefore, hsa_circRNA_001587 inhibits PC cell migration, invasion, angiogenesis and tumorigenesis by impairing miR-223-mediated SLC4A4 inhibition. Human circular (hsa_circ)RNA_001587 and solute carrier family 4 member 4 (SLC4A4) are poorly expressed but microRNA (miR)R-223 is overexpressed in pancreatic cancer (PC) cells. hsa_circRNA_001587 binds to miR-223. Overexpression of hsa_circRNA_001587 inhibits PC progression. Overexpression of miR-223 downregulates the expression of SLC4A4 and promotes PC cell growth. hsa_circRNA_001587 may be a potential target for PC treatment.