Proangiogenic role of circRNA‐007371 in liver fibrosis

• Published in: Cell proliferation Vol. 56; no. 6; pp. e13432 - n/a
• Main Authors: Zhao, Chong, Qian, Shuaijie, Tai, Yang, Guo, Yangkun, Tang, Chengwei, Huang, Zhiyin, Gao, Jinhang
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.06.2023; John Wiley and Sons Inc
• Subjects: Angiogenesis; Animal models; Animals; Antiangiogenics; Argonaute 2 protein; Blood vessels; Carbon tetrachloride; Cell adhesion & migration; Cell migration; Cell proliferation; Circular RNA; Cirrhosis; Collagen; Data analysis; DNA microarrays; Fibrosis; Gene expression; Gene sequencing; Humans; Immunoprecipitation; Liver; Liver cancer; Liver cirrhosis; Liver Cirrhosis - chemically induced; Liver Cirrhosis - genetics; Liver diseases; Mice; MicroRNAs; MicroRNAs - genetics; miRNA; Original; Proteins; Ribonuclease; Ribonucleic acid; RNA; RNA, Circular - genetics; Software; Sponges; Statistical analysis; Thioacetamide; Vascular endothelial growth factor
• ISSN: 0960-7722; 1365-2184
• DOI: 10.1111/cpr.13432

Circular RNAs (circRNAs) are crucially involved in cancers as competing endogenous RNA (ceRNA) or microRNA (miRNA) sponges. However, the function and mechanism of circRNAs in liver fibrosis remain unknown and are the focus of this study. Murine fibrotic models were induced by thioacetamide (TAA) or carbon tetrachloride (CCl4). Increased angiogenesis is accompanied by liver fibrosis in TAA‐ and CCl4‐induced murine fibrotic livers. circRNA microarray and argonaute 2 (AGO2)‐RNA immunoprecipitation (RIP) sequencing (AGO2‐RIP sequencing) were performed in murine livers to screen for functional circRNAs. Compared to control livers, 86 differentially expressed circRNAs were obtained in TAA‐induced murine fibrotic livers using circRNA microarray. In addition, 551 circRNAs were explored by AGO2‐RIP sequencing of murine fibrotic livers. The circRNA‐007371 was then selected and verified for back‐spliced junction, resistance to RNase R, and loop formation. In vitro, murine hemangioendothelioma endothelial (EOMA) cells were transfected with circRNA‐007371 overexpressing plasmid or empty plasmid. circRNA‐007371 overexpression promoted tube formation, migration, and cell proliferation of EOMA cells. RNA sequencing and miRNA sequencing were then performed to explore the mechanism of the proangiogenic effects of circRNA‐007371. circRNA‐007371 promotes liver fibrosis via miRNA sponges or ceRNA mechanisms. Stag1, the parent gene of circRNA‐007371, may play a significant role in proangiogenic progression. In conclusion, circRNA‐007371 enhances angiogenesis via a miRNA sponge mechanism in liver fibrosis. The antiangiogenic effect of circRNA‐007371 inhibition may provide a new strategy for treating patients with liver cirrhosis. The expression profiling of circRNA with ceRNA function in the murine fibrotic liver was displayed. A new circRNA, circRNA‐007371, which contributed to the pathogenesis of liver fibrosis, was verified. A new mechanism by which circRNA‐007371 promoted angiogenesis as a miRNA sponge was discovered.