Table 3 Role of extracellular miRNAs in intestinal disease and homeostasis

IBD patients (UC and CD)

Human

Mast cells

IECs

↑miR-223

↓CLDN8, Occludin and ZO-1

Destroyed intestinal barrier functions

¹⁰⁰

Short bowel syndrome

Rats

IECs

Intestinal cells

↑miR-125a/b

↑Cleaved caspase 3,

↓MCL1

Inhibited IECs proliferation and promoted apoptosis

¹⁷²

Allogeneic small bowel transplantation model

Rat

HO-1-modified bone marrow mesenchymal stem cell

IECs

↑MiR-200b

Downregulated HMGB3/JNK signaling,

↓ZO-1 and Cleaved caspase-3

Alleviated inflammatory injury, and apoptosis, and decreased damage to intercellular TJ structures

⁹⁹

DSS-induced colitis

Mice

Human umbilical cord mesenchymal stem cell

Monocytes

↑miR-378a-5p

Inhibited NLRP3, IL-18, IL-1β, and Caspase-1 cleavage

Abrogated cell pyroptosis and inflammation

⁹⁷

Rab27A-dependent CD11c+ myeloid cell and IBD patients (UC and CD)

Mice and Human

Dendritic cells (CD11c+ cells)

Macrophages and T cells

↑miR-146a, miR-221, and miR-222

Rab27-dependent TRAF6, IRAK-1, and NLRP3 signaling

Controlled inflammatory immune cell functions, and protected crypt loss

¹⁷³

DSS-induced colitis

Mice

M2 Macrophage

IECs

↑miR-590-3p

Inhibited LATS1/YAP/β-Catenin Signaling

Controlled mucosal damage and epithelial repair

⁹⁵

TNBS-induced or IL-10 KO colitis and CD patients

Mice and Human

IECs

N/A

↓miR-141

↑CXCL12β/total-CXCL12

Increased intestinal inflammation via affecting inflammatory cell trafficking

¹⁷⁴

Adherent-invasive E. coli infection

Human

IECs

IECs

↑miR-30c and miR-130a

Inhibited ATG5 and ATG16L1

Inhibited autophagy

¹⁷⁵

Enterotoxigenic Bacteroides fragilis (IBD, CRC and DSS)

Human and Mice

Colorectal cancer cells

Colorectal cancer and Th17 cells

↓miR-149-3p

↑PHF5A and KAT2A

Modulate Increased Th17 cell differentiation, intestinal inflammation, and CRC development

¹⁷⁶

Colorectal cancer and Tumor-induced animal model

Human and Mice

Colorectal cancer cells

Colorectal cancer cells

↑miR-25

SIRT6-mediated inhibition of the Lin28b/NRP-1 axis

Colorectal cancer progression and metastasis.

¹⁷⁷

Substance P/NK-1R signaling activation

Human and Mice

IECs

N/A

↑miR-21 and ↓miR-320

N/A

Promoted cell proliferation and migration of colonic epithelial cells and colonic crypts

¹⁰¹

Mesenchymal stem cells modified by the fusion gene iRGD-Lamp2b

Human and Mice

Cord blood mesenchymal stem cells

NRP-1-positive colon cancer cells

↑miRNA-221

N/A

Inhibited colon cancer cell proliferation, and suppressed tumor growth

¹⁷⁸

Colorectal adenocarcinoma

Human and Mice

Cancer-associated fibroblasts

Colorectal carcinoma cell line and umbilical vein endothelial cells

↑miR-135b-5p

Downregulates FOXO1

Promoted tumor proliferation, migration, and angiogenesis

¹⁷⁹

Cryptosporidium parvum infection (IBD)

Human

IECs

Pathogens

↓miRNA F

TLR4-dependent IKK2-SNAP23 signaling

Increased delivery of anti-microbial peptides to inhibit the pathogen, revealing a new arm of mucosal immunity.

¹⁰⁶

Inflammatory disease

Human

Foxp3+ T regulatory cells

Th1 cells

↑miRNA let-7d

Ptgs2 (Cox-2)

Suppressed Th1 cell proliferation and cytokine secretion and prevented systemic infection

¹⁸⁰

DSS-induced colitis

Mice

IECs

Macrophages

miR-433-3p

MAPK

Prevented inflammatory factors, and restore homeostasis in the intestinal microenvironment

¹⁸¹

IBD patients

Human

IECs

N/A

miR-23a and miR-155

N/A

Decreased effects of PMNs and enhanced tissue healing

¹⁸²

DSS-induced colitis

Mice

Mesenchymal stem cells

Macrophages

miR-203a-3p.2

Caspase 11/4

Ameliorated colitis

¹⁸³

TNBS-induced colitis

Mice

Bone-marrow mesenchymal stem cells

N/A

miR-146a

Inhibits TRAF6, IRAK1, and NF-κB

Inhibited inflammatory cytokines and ameliorated colitis

¹⁸⁴