Microbial Disruption of Autophagy Alters Expression of the RISC Component AGO2, a Critical Regulator of the miRNA Silencing Pathway

Inflammatory Bowel Diseases
Michal SibonyNicola L Jones

Abstract

Autophagy is implicated in Crohn's disease (CD) pathogenesis. Recent evidence suggests autophagy regulates the microRNA (miRNA)-induced silencing complex (miRISC). Therefore, autophagy may play a novel role in CD by regulating expression of miRISC, thereby altering miRNA silencing. As microbes associated with CD can alter autophagy, we hypothesized that microbial disruption of autophagy affects the critical miRISC component AGO2. AGO2 expression was assessed in epithelial and immune cells, and intestinal organoids with disrupted autophagy. Microarray technology was used to determine the expression of downstream miRNAs in cells with defective autophagy. Increased AGO2 was detected in autophagy-deficient ATG5-/- and ATG16-/- mouse embryonic fibroblast cells (MEFs) in comparison with wild-type MEFs. Chemical agents and VacA toxin, which disrupt autophagy, increased AGO2 expression in MEFs, epithelial cells lines, and human monocytes, respectively. Increased AGO2 was also detected in ATG7-/- intestinal organoids, in comparison with wild-type organoids. Five miRNAs were differentially expressed in autophagy-deficient MEFs. Pathway enrichment analysis of the differentially expressed miRNAs implicated signaling pathways previously ass...Continue Reading

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Citations

Oct 8, 2016·Autophagy·Lisa B FrankelAnders H Lund
Apr 10, 2017·Digestive Diseases and Sciences·Bo CaoLiu Hong
Jun 7, 2020·International Journal of Molecular Sciences·Vasiliki I PantazopoulouEma Anastasiadou
Sep 12, 2020·Cell Proliferation·Jiali LongWei Zhu
Feb 16, 2019·Journal of Biomedical Science·Sabah HaqWaliul I Khan
May 2, 2017·Frontiers in Oncology·Devrim GozuacikMuhammed Kocak
Nov 8, 2017·Inflammopharmacology·Priyanka MishraBhuvnesh Kumar

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Methods Mentioned

BETA
genotyping
scraping
electrophoresis
confocal microscopy

Software Mentioned

GraphPad Prism
FluorChem FCII
R
Partek Genomics Suite
Ingenuity

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