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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.

Intestinal mucosal injury is one of the most significant complications of burns. In our previous study, it was found that autophagy could alleviate burn‐induced intestinal injury, but the underlying mechanisms are still unclear. Irregular expression of long noncoding RNAs (lncRNAs) is present in many diseases, including burns. However, the relationship between lncRNAs and intestinal mucosal injury requires further elucidation. In this study, we established a burn mice model and detected the expression level of autophagy‐related proteins. Then, H19 content after autophagy intervention was tested in vitro and in vivo. The interaction of H19 with Let‐7g and that of Let‐7g with epidermal growth factor (EGF) were verified by dual‐luciferase reporter assays. We found that the expression of the autophagy‐associated proteins LC3‐II and Beclin‐1 was raised in the intestinal tract of the burn mice model. Similarly, the transfection of H19 raised autophagy levels. H19 was elevated after autophagy intervention in vitro and in vivo. H19 overexpression was able to promote IEC‐6 cell migration and proliferation. Let‐7g was suppressed by the overexpression of H19 and the combination of Let‐7g mimic was able to abolish the physiological effect of H19. Moreover, the suppression of Let‐7g increased the expression of EGF protein, which heightened IEC‐6 cell migration and proliferation. Besides this, dual‐luciferase assays revealed that Let‐7g was a direct target of H19 as well as the EGF gene. Taken together, autophagy‐mediated H19 increases in mouse intestinal tract after severe burn and functions as a sponge to Let‐7g to regulate EGF, which suggests that H19 serves as a potential therapeutic target and biomarker for intestinal mucosal injury after burns.

To investigate the regulation of epidermal growth factor (EGF) by autophagy‐mediated long non‐coding RNA (lncRNA) H19 in the intestinal tracts of severely burned mice. C57BL/6J mice received third‐degree burns to 30% of the total body surface area. Rapamycin and 3‐methyladenine (3‐MA) were used to activate and inhibit autophagy, and the changes in LC3 and Beclin1 levels were assessed by Western blotting. The effect of autophagy on lncRNA H19 was detected by qRT‐PCR. Adenovirus‐mediated overexpression of lncRNA H19 in IEC‐6 cells was used to assess the effects of lncRNA H19 on EGF and let‐7g via bioinformatics analysis, Western blotting and qRT‐PCR. let‐7g mimic/inhibitor was used to overexpress/inhibit let‐7g, and qRT‐PCR and Western blotting were used to detect the effects of let‐7g on EGF. The expression levels of LC3‐II, Beclin1 and lncRNA H19 were increased in intestinal tissues and IEC‐6 cells after rapamycin treatment but were reversed after 3‐MA treatment. LC3‐II, Beclin1 and lncRNA H19 levels increased in intestinal tissues after the burn, and these increases were more significant after rapamycin treatment but decreased after 3‐MA treatment. The lncRNA H19 overexpression in IEC‐6 cells resulted in increased and decreased expression levels of EGF and let‐7g, respectively. Furthermore, overexpression and inhibition of let‐7g resulted in decreased and increased expression of EGF, respectively. Taken together, intestinal autophagy is activated after a serious burn, which can increase the transcription level of lncRNA H19. lncRNA H19 may regulate the repair of EGF via let‐7g following intestinal mucosa injury after a burn.