Table 3.

Several classical mirnas involved in macrophage polarization.

miRNA	Phenotype promoted	Targets	Mechanism of Action	Ref.
miR-9	M1	PPARδ	MiR-9 targets the regulation of PPARδ in M1 macrophages, thereby blocking its anti-inflammatory effect.	[104]
miR-155	M1	SHIP1,PI3K/AKT, C/EBPβ	MiR-155 promotes inflammation by inhibiting the expression of SHIP1, an inhibitor of the PI3-AKT signaling pathway.	[105]
Let-7c	M2	C/EBP-δ,PAK1	Let-7c is expressed at a higher level in M2 macrophages, and inhibiting C/EBP-δ enhances anti-inflammatory polarization of M2; Let-7c inhibits the expression of PAK1, thus inhibiting the activation of the NF-κB pathway and thereby reducing the manifestation of inflammatory factors associated with M1.	[106,107]
miR-127	M1	Bcl6, JNK pathway	MiR-127 targets B-cell lymphoma 6 (Bcl6) and promotes activation of the JNK signaling pathway, thereby enhancing the development of pro-inflammatory macrophages.	[108]
miR-34a	M2	Notch3	MiR-34a inhibits LPS-induced inflammatory responses via targeting Notch34.	[109]
miR-124	M2	STAT3,TACE	MiR-124 targets STAT3 reduced IL-6 production, targets TACE to reduce mature TNF-α production, thereby acting anti-inflammatory.	[110]
miR-146a	M2	TRAF1,IRAK146	MiR-146 targets IRAK1 and TRAF6, inhibiting the activity of the NF-κB pathway and hence reducing inflammatory reactions.	[111]
miR-21	M2	/	MiR-21 is positively regulated downstream of CSF-1R pTyr-721, promoting the expression of the M2 macrophage gene.	[112]
miR-21	M1	STAT3	MiR-21 targeting STAT3 enhances M1 macrophage polarization while inhibiting M2 macrophage polarization.	[113]
miR-223	M2	STAT3	MiR-223 inhibits the production of the pro-inflammatory cytokines IL-6 and IL-1β, but not TNF-α, through regulating the activation of STAT3 in macrophages.	[114]