Compromise Of Autophagy By MIR30B Benefits The Intracellular Survival Of Helicobacter Pylori

Helicobacter pylori (H. pylori) is a major causative agent of chronic gastritis andpeptic ulcer,and a risk factor for gastric cancer and gastric mucosal lymphoid tissuelymphoma. Helicobacter pylori chronic persistent infection plays a key role in itscause-related disease process. Clinical treatment program for H. pylori can not completelyclear the bacteria, but also there is serious drug resistance and toxicity. Although H. pyloriis generally considered as an extracellular microorganism, a growing body of evidencesupports that at least a subset of H. pylori has an intraepithelial location and that a minorfraction of H. pylori resides inside gastric epithelial cells. Though strong cellular immunityis induced by H. pylori infection, the immune responses and antibiotic are unable to clearthe bacteria, resulting in bacterial persistence. Thus, to clarify the mechanism of H. pylorichronic infection, there is an important clinical and theoretical significance for developingnew drugs and treatments for H. pylori infection.Autophagy is a lysosomal degradation pathway that is essential for survival,differentiation, development, metabolism, and principally serves an adaptive role to protectorganisms against diverse pathologies. Autophagy plays an important role in resistance ofthe infection and inflammation induced by pathogenic microorganisms. Intriguingly, thesecurrent studies revealed that autophagy induced by H. pylori in gastric epithelium cells, andplays an important role in clearing intracellular H. pylori.Single-stranded endogenous non-coding RNA molecules of19–24nucleotides, knownas microRNAs (miRNAs), can specifically bind to3′UTRs of target cellular mRNA in turntriggering mRNA degradation or inhibition of translation, resulting in regulating gene atpost-transcriptional levels. Previous studies indicated that H. pylori infection could inducethe expression of MIR30B in gastric epithelial cells. After confirmed that H. pylori infectioninduced autophagy, we observed that MIR30B significantly attenuated MAP1LC3B-IIconversion and decreased formation of GFP-MAP1LC3B dots in AGS cells upon H. pyloriinfection. These results suggest that MIR30B may regulate autophagy induced by H. pylori. How MIR30B does decrease autophagy? BECN1and ATG12, as both of important proteins,play a key role in regulating autophagy. In a screen for MIR30B targets, ATG12andBECN1were identified as putative MIR30B target genes by using TargetScan. Thus, wewonder that compromised autophagy in gastric epithelial cells is whether or not MIR30Bregulate BECN1and ATG12signaling pathway.Therefore, the first part of this paper will explore the mechanism that MIR30B regulateautophagy induced by H. pylori in gastric epithelial cells and persistent infection. MIR30Bdisrupted autophagy by inhibiting the expression of key autophagy genes BECN1andATG12, leading to subverting host autophagic responses for H. pylori survival or growth.With up-or down-regulating the expression of MIR30B, we detected autophagy and theintracellular bacteria, and opened a new avenue of research model the potential of miRNAsto modulate autophagy in H. pylori infection. This paper may clarify the mechanism thatMIR30B regulate autophagy induced by H. pylori in gastric epithelial cells and persistentinfection, and provide a theoretical basis for new treatment of H. pylori chronic persistentinfection. Conclusion as following:1. H. pylori could reside and survive inside gastric epithelial cells. This may be animportant reason for H. pylori persistent infection.2. H. pylori induced overexpression of MIR30B. In addition, we firstly observed thatautophagy decreases in patients with chronic H. pylori infection compared withnone-infected individuals.3. ATG12and BECN1are novel targets of MIR30B. Moreover, MIR30B maydown-regulate ATG12and BECN1expression through mRNA degradation. Our findingsprovide a novel mechanism in which compromised autophagy by MIR30B benefits theintracellular survival of H. pylori.4. Inverse correlation between MIR30B and ATG12/BECN1expression in H.pylori-positive human samples.5. MIR30B, as a new class of negative feedback regulator in autophagy pathway,regulates autophagy in H. pylori infection. These results establish a novel pathogenicmechanism for H. pylori persistent infection, and provide a new avenue of research onpathogenic mechanism of H. pylori.As the earlier reaction of the cells receiving exogeous and endogenous pressure, miRNAs are involved in modulating immune response. Gastric epithelium cells are the firstline of defense against invading microbes, and they protect themselves through innateimmune response. However, the regulatory role of miRNAs in bacteria infection andimmunity is not clear. Therefore, the second part of this paper will explore the mechanismthat MIR155negatively regulated inflammation by targeting a key adaptor moleculeMYD88in inflammatory pathways. This paper opens a new avenue of research model thepotential of miRNAs to modulate inflammation in H. pylori infection, and provides atheoretical basis for new treatment of H. pylori induced inflammation.