Background Circular RNA (circRNA) plays key regulatory roles in the development of many diseases. However the biological functions and potential molecular mechanisms of circRNA in the injury and repair of intestinal mucosa in mice after severe burns are yet to be elucidated. Methods Cell counting kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), wound healing and transwell assays were used to detect cell proliferation and migration ability. Real-time quantitative PCR was used to identify the expression of circRNA, microRNA and messenger RNA. Nuclear and cytoplasmic separation experiments were employed to perceive the location of circRNA_Maml2. Finally, in vitro and in vivo experiments were conducted to study the repairing effect of circRNA_Maml2 on the intestinal mucosa of mice after severe burns. Results When compared with the control group, the expression of circRNA_Maml2 was significantly reduced in the severe burn group. Furthermore, overexpression of circRNA_Maml2 promoted the proliferation and migration of CT26.wt cells in vivo and the repair of damaged intestinal mucosa in vitro. CircRNA_Maml2 acted as a sponge adsorption molecule for miR-93-3p to enhance the expression of frizzled class receptor 7 and activate the downstream Wnt/β-catenin pathway, thereby promoting the repair of the intestinal mucosa. Conclusions Our findings demonstrate that circRNA_Maml2 regulates the miR-93-3p/FZD7/Wnt/β-catenin pathway and promotes the repair of damaged intestinal mucosa. Hence, circRNA_Maml2 is a potential therapeutic target to promote intestinal mucosal repair.
Circular RNA (circRNA) is a novel noncoding RNA that is mostly found in humans and animals. Although the flux of circRNA research has increased in recent years, its precise function is still unclear. Some studies demonstrate that circRNAs can function as microRNA (miRNA) sponges involved in the regulation of competitive endogenous RNAs networks and play a crucial role in many biological processes. Other studies show that circRNAs play multiple biological roles in gastrointestinal diseases. However, the expression characteristics and function of circRNA in intestinal mucosal injury and repair after severe burn have not been reported. This study aims to screen differentially expressed circRNAs in intestinal mucosal injury and repair after severe burns and understand their underlying mechanisms. To test our hypothesis that circRNA may play a role in promoting repair in intestinal mucosa injury after severe burns, we collected the intestinal tissues of three severely burned mice and three pseudo‐scalded mice and evaluated the expression of circRNAs via microarray analysis. Quantitative real‐time polymerase chain reaction was also used to validate the circRNA microarray data by selecting six based on different multiples, original values, and p values. The host genes of all differentially expressed circRNAs and the downstream target genes of six selected DEcircRNAs were identified by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Meanwhile, we also created a circRNA‐miRNA‐mRNA network to predict the role and function of circRNAs in intestinal mucosal injury and repair after severe burns.
Intestinal mucosal injuries are directly or indirectly related to many common acute and chronic diseases. Long non-coding RNAs (lncRNAs) are expressed in many diseases, including intestinal mucosal injury. However, the relationship between lncRNAs and intestinal mucosal injury has not been determined. Here, we investigated the functions and mechanisms of action of lncRNA Bmp1 on damaged intestinal mucosa. We found that Bmp1 was increased in damaged intestinal mucosal tissue and Bmp1 overexpression was able to alleviate intestinal mucosal injury. Bmp1 overexpression was found to influence cell proliferation, colony formation, and migration in IEC-6 or HIEC-6 cells. Moreover, miR-128-3p was downregulated after Bmp1 overexpression, and upregulation of miR-128-3p reversed the effects of Bmp1 overexpression in IEC-6 cells. Phf6 was observed to be a target of miR-128-3p. Furthermore, PHF6 overexpression affected IEC-6 cells by activating PI3K/AKT signaling which was mediated by the miR-128-3p/PHF6 axis. In conclusion, Bmp1 was found to promote the expression of PHF6 through the sponge miR-128-3p, activating the PI3K/AKT signaling pathway to promote cell migration and proliferation.
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