MicroRNAs as Immunotherapy Targets for Treating Gastroenterological Cancers

Table 1

miRNAs involved in immunity and immunotherapy for gastroenterological cancers.

Cancer types/cell type	MicroRNAs	Target genes	Immunological component/process	References
Hepatocellular Carcinoma	miR-34a	DAPK2/SP1 pathway	Dendritic cell activation	[74]
	miR-34a	PD-L1	PD-1/PD-L1 immune checkpoint blockade	[75]
	miR-146a	Effector of STAT3	NK cells and anti-tumor lymphocytes	[76]
	miR-20a, miR-93 and miR-106b	MICA/B	Antigen presentation and immune evasion	[79]
	miR-101	DUSP1	Proinflammatory factors and tumor-associated macrophages	[82]
	miR-26a	Macrophage colony-stimulating factor (M-CSF)	Chemokine ligand (CCL) 22, IL10 and macrophage infiltration	[84]
	miR-122	HCV genome	Assisting replication of HCV	[86]
	miR-122	Cyclin G1	Inhibiting transcription of HBV	[88]
	miR-122	Suppressor of cytokine signaling 3 (SOCS3)	Interferon production	[89]
	miR-122	Chemokine (C-C motif) ligand 2 (CCL2)	Gr1^+ immune cells recruitment, proinflammatory cytokine production	[90]
	miR-185	LDLR, SCD1, SCARB1 and SREBP2	HCV replication	[91]
	miR-130b	LDLR, lipid metabolism pathway	HCV replication; reinforcing the antiviral activity of 25-hydroxycholesterol (25-HC),	[91]
Pancreatic Cancer	miR-203	Toll-Like Receptor 4	Modulating TLR-mediated immune response and facilitate immune escape	[92]
	miR-142-5p	PD-L1	PD-1/PD-L1 immune checkpoint blockade	[93]
	miR-454	Stromal cell derived factor-1	Macrophage recruitment and dendritic cell maturation	[94]
	miR-206	Chemokines (C-X-C motif) ligand 1 and (C-C motif) ligand 2, Interleukin-8 and the granulocyte macrophage colony-stimulating factor	Inhibiting inflammation and immune reaction	[95]
	miR-206	Vascular endothelial growth factor C	Inhibiting blood and lymphatic vessel formation	[95]
	miR-9	unknown	Inflammation of acute pancreatitis	[96]
	miR-216a	PTEN, Smad7, pAkt and TGF-β receptor 1	Inflammation of acute pancreatitis	[97]
	miR-146a	IL-1b, IL-6 and TNF-a	Inflammation of chronic pancreatitis	[98]
Colorectal Cancer	miR-222 and -339	ICAM-1	Promotes cytotoxicity of CTL's	[99]
	miR-21	PDCD4	IL-10 transcription and CD3^+ and CD45RO^+ cell selection	[100]
	miR-17-5p and -20a	STAT3	Decreased burden from reactive oxygen species and inhibition of MDSC immunosuppression	[101, 102]
	miR-124	STAT3	Decreased progression of ulcerative colitis	[103]
	miR-19b	HIF-alpha	Anti-inflammatory in Crohn's disease	[104]
	miR-494	PTEN	Increased number of pro-cancer MDSC's
	miR-484 and -19a	CD137L	Decreased PI3K/mTOR signaling and IL-8 production	[105]
	miR-142-5p	PD-L1	Increased viability of CTL's	[93]
	miR-20b, -21, and -130b	PTEN	PD-L1 overexpression and CRC proliferation	[101, 106]
Gastric Cancer	miR-34a	DAPK2/SP1	Increased dendritic cell immune response	[74]
Gallbladder Cancer	miR-218-5p	Downregulated by lncRNA CCAT1	Modulation of the tumor micro-environment	[107]
	miR-155	IFNγ	Activation and proliferation of CD4^+ and CD8^+ T cells	[108]
	miR-133a-3p	Recombination signal-binding protein Jκ	Differentiation of T cell lineage from common lymphoid precursor.	[109]
	miR-1, miR-133, miR-143 and miR-145	VEGF-A, ErbB3, AXL	Modulation of the tumor micro-environment	[110]
Esophageal Cancer	miR-31	STK40	Inflammatory signaling	[111]
	miR-34a	Upregulated by NF-kappaB	Inflammation signaling	[112]
	miR-155	SOCS1/JAK/STAT pathway	Normal function of Kupffer cells	[113]
	miR-21	Exosomal miRNA	T cells and macrophages activation	[114]