The Role of Autophagy and Related MicroRNAs in Inflammatory Bowel Disease

Table 1

Summary of miRNAs that regulate autophagy in IBD.

MicroRNA	Samples	Diseases		Target	Effects on autophagy	Potential mechanism	Years and references
		CD	UC
miR-142-3p^※	HCT116	+	−	ATG16L1, NOD2	Inhibit	Decreases ATG16L1 mRNA and protein levels; modulates NOD2-dependent autophagy; inhibits IL8 mRNA expression.	2014 [30]; 2018 [40]
miR-320	HT-29	+	+	NOD2, NF-κB	Inhibit	Downregulates NOD2 expression.	2016 [31]
miR-192^※	HCT116	+	−	NOD2, NF-κB	Inhibit	Downregulates NOD2 expression; suppresses NF-κB activity.	2014 [33]
miR-122	HT-29	+	−	NOD2, NF-κB	Inhibit	Suppresses NOD2; increases NF-κB activity.	2017 [35]; 2013 [36]
miR-93; miR-106B	Human colon tissues, HCT116	+	−	ATG16L1; PTEN	Inhibit	Targets ATG16L1 messenger RNA; reduces levels of ATG16L1; prevents autophagy-dependent eradication of intracellular bacteria; suppresses PTEN by enhancing activity of the PI3K/Akt pathway.	2014 [41]; 2017 [98]
miR-30C; miR-130a	Human intestinal epithelial T84 cells/mice enterocytes	+	−	ATG5,; ATG16L1; mTOR	Inhibit	Reduced levels of ATG5 and ATG16L1; miR-130a increases levels of p-mTOR; impairs LC3-II accumulation.	2014 [44]; 2017 [43]
miR-346	Human intestinal epithelial cells	+	+	Vitamin D receptor (VDR); GSK3B	Upregulate	Downregulates VDR, leading to upregulation of ATG16L1; activates autophagy by interrupting the association between BCL2 and BECN1 in a GSK3B-dependent manner.	2014 [46]; 2018 [68]
miR-20a	Human colonic mucosal tissues	+	−	BECN1,; ATG16L1,; SQSTM1	Inhibit	Downregulates BECN1, ATG16L1, and SQSTM1.	2017 [47, 48]
MiR-196^※	Human epithelial cells	+	−	LC3-II, IRGM	Inhibit	Inhibits accumulation of LC3-II.	2011 [53]
miR-665	Human/mice colonic mucosal tissues.	+	+	XBP1, ORMDL3	Induce	Represses XBP1 and ORMDL3 expression.	2017 [65]
miR-150	Intestinal tissue serum	−	+	c-Myb	Unclear	Inhibits c-Myb, leading to decreased αSMA; exhibits antifibrotic effects.	2016 [69]
miR-146b	Mice colonic tissues.	−	+	siah2; FOXO3	Inhibit	Decreases expression of siah2; activates the NF-κB pathway.; Decreases siah2 and FOXO3 expression.	2013 [76]; 2016 [99]
miR-221-5p	Human colonic epithelial cells	+	+	Substance P	Inhibit	SP regulates miR-221-5p expression through the MAPK and NF-κB pathways; miR-221-5p negatively regulates expression of proinflammatory cytokines in colonic epithelial cells in response to SP.	2014 [79]
miR-132; miR-223	Human/mice colonic tissues	+	+	FOXO3a, JNK	Inhibit	Suppresses the level of IκBα through downregulation of FOXO3a, leading to enhanced NF-κB signaling; JNK signaling induces miR-223.	2016 [80]; 2015 [81]
miR-155^※	Mice colonic tissues	−	+	SHIP-1, FOXO3a; PI3K-Akt pathway	Inhibit	Increases Akt activation by decreasing SHIP-1 expression, leading to upregulation of mTOR; downregulates FOXO3a, leading to enhanced NF-κB signaling; activates the PI3K-Akt pathway.	2017 [87]; 2015 [75]; 2012 [89]
miR-21^※※	Mice colonic tissues.	−	+	Akt, m-TOR, JNK, PTEN	Inhibit/induce	Unclear/decreases phosphorylated AKT and deactivates the mTOR; NK-1/c-Jun pathway; promotes miR-21 upregulation.; miR-21 inhibition enhances PTEN protein levels and inhibits AKT phosphorylation.; Inhibits autophagy via the PTEN/Akt/mTOR pathway.	2013 [90, 96]; 2015 [95]; 2014 [82]; 2018 [97]

※ refers to more closely related to IBD; ※※ refers to the most studied in IBD [8, 16, 25].