PRP8-Induced CircMaml2 Facilitates the Healing of the Intestinal Mucosa via Recruiting PTBP1 and Regulating Sec62

Abstract

Background: Multiple organ dysfunction syndrome(MODS) occurs in the gastrointestinal tract and injured intestinal mucosa is the anatomical basis for various diseases. The expression of circular RNAs (circRNAs) is implicated in many diseases; however, the role of circRNAs in intestinal mucosal injury is yet to be discovered. Our preliminary gene microarray analysis revealed a novel circular RNA, circMaml2, with a significant intestinal mucosal protection effect. Its expression was found to decrease in severely burned intestinal mucosal tissue, whereas its overexpression might facilitate the reconstruction of the injured intestinal mucous membrane. Methods: The function of circMaml2 in cell proliferation and migration was studied in MC38 cells. The repair function of circMaml2 was tested on the intestinal mucosa of mice. RNA-binding protein polypyrimidine tract-binding protein 1(PTBP1) was selected by pull-down assay and mass spectrometry (MS). RNA immunoprecipitation (RIP) was performed to confirm the binding of circMaml2 and PTBP1 and to study PTBP1 and its downstream target, early B-cell factor 1(Ebf1). Bioinformatics software forecast analysis and dual-luciferase reporter assay were performed to ascertain miR-683 and Sec62 as the downstream targets of circMaml2 and miR-683, respectively. Furthermore, PRP8 was discovered to promote the biogenesis of circMaml2. Results: CircMaml2 promotes cell proliferation and migration of MC38 cells and the repair of the intestinal mucosa of mice. This effect is brought about by combining with PTBP1 to improve Ebf1 and interacting with miR-683 to regulate Sec2. Furthermore, PRP8 was discovered to promote the biogenesis of circMaml2. Conclusion: This is the first reported study of the effect of circMaml2 on intestinal mucosal repair.

Circular RNA Cdr1as inhibits proliferation and delays injury-induced regeneration of the intestinal epithelium

“…This repression of miR-195 expression in Cdr1as -/mice is crucial for controlling epithelial regeneration, since Cdr1as-mediated inhibition of epithelial repair after wounding in vitro and disrupted growth of intestinal organoids ex vivo were almost totally abolished by miR-195 silencing. In support of the present findings, several circRNAs were recently found to play an important role in maintaining the intestinal epithelial integrity and defense (42)(43)(44). circHIPK3 enhanced intestinal epithelial repair after acute injury and promoted constant renewal of the epithelium by reducing miR-29b function, but its tissue levels in intestinal mucosa decreased significantly in patients with IBD (14).…”

“…circHIPK3 enhanced intestinal epithelial repair after acute injury and promoted constant renewal of the epithelium by reducing miR-29b function, but its tissue levels in intestinal mucosa decreased significantly in patients with IBD (14). circMaml2 facilitated healing of the intestinal mucosa via recruiting PTBP1 and regulating Sec62 (42), and circPABPN1 modulated intestinal epithelium host defense by altering translation of autophagy-associated protein ATG16L1 through interaction with HuR (33).…”