Study On The Role And Related Mechanism Of Long Noncoding RNA H19 In The Progression Of Ulcerative Colitis

Background and aimUlcerative colitis(UC),belonging to inflammatory bowel diseases(IBD),is characterized by chronic inflammatory disorder of the gastrointestinal tract and most often orrcurs repeatly.Currently,the precise etiology of UC has not been clarified.Studies have shown that IBD occurs in genetically susceptible individuals.The etiology is multifactorial,involving environmental factors,intestinal dysbiosis,and immune-imbalance.Intestinal inflammation is associated with intestinal mucosal permeability caused by intestinal barrier damage.Here,we aim to explore the role of long non-coding RNA H19(LncRNA H19)in ulcerative colitis,so as to provide new ideas and basis for the progression of UC.MethodsPatients with UC confirmed via endoscopy or surgery in Jinling hospital from March 2021 to February 2022 were recruited.Base-line data and colonic mucosal samples were collected from patients with UC(n=25)and healthy subjects(HC)(n=25).HE staining was used to assess the degree of mucosal injury,and qRT-PCR was used to analyze the expression levels of LncRNA H19 and PKM2 in intestinal mucosa.In Caco-2,results from RNA pull-down and RIP verified the correlation between LncRNA H19 and PKM2.Moreover,PKM2,Occludin and Wnt signaling pathway-related proteins were detected by Western blot.Results1.H19 was significantly higher in the colonic mucosa of patients with UC than thatin healthy controls(P<0.05),and PKM2 decreased in the colonic mucosa of patients with UC than that in healthy controls.H19 was significantly correlated with the severity of the disease among UC patients(P<0.05).The area under the ROC curve of LncRNA H19 in predicting UC was 0.811(95%CI:0.694-0.928).2.The intestinal barrier of UC patients has been severely dampened.3.H19 plays a post-transcriptional regulatory role by binding to PKM2 protein.4.Western blot showed that after stimulating with LPS(500ng/mL)at 12h,the expression of PKM2,C-myc,β-catenin,CyclinD1,and Occludin decreased significantly,which was significantly attenuated by transfected with siRNA H19.While the expression of PKM2,C-myc,β-catenin,CyclinD1,and Occluding decreased more significantly after transfected with H19 mimics.Conclusion1.The tissue structure of intestinal mucosa in UC patients was seriously damaged,characterized by the increased expression of LncRNA H19 and decreased expression of PKM2.H19 is significantly correlated with the severity of UC patients.2.LncRNA H19 dampens intestinal mucosal barrier via PKM2/Wnt signaling pathway in vitro,which may be one of the underlying mechanisms of UC progression.