Table 1 Role of miRNAs in FMF pathogenesis: expression profile and reported mechanisms of action

↑: miR-144-3p, miR-21-5p, miR-4454, and miR-451a

↓: miR-107, let-7d-5p, and miR-148b-3p

Inflammation

Let-7d-5p represses the proliferation of Th1 cells and IFN- γ release [79]

N/A

N/A

Amarilyo et al. (2018) [93]

miR-107 acts on CDK6. Upon LPS stimulation, miR-107 is downregulated which promotes the expression of CDK6 and adhesion of macrophages [115]

N/A

N/A

miR-148b-3p suppresses the production of IL-12, IL-6, and TNF-α [95]

N/A

N/A

↑: miR-34a-5p, miR-142-3p, miR-216a-5p, miR-340-5p, miR-429, and miR-582-5p

↓: miR-107, miR-569, and miR-1304-5p

Inflammation

miR-34a-5p activates nuclear factor erythroid-2 related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway and reduces inflammation [116]

N/A

N/A

Kahraman et al. (2021) [97]

↓ miR-204-3p

Inflammation

IGFBP2/AKT/Bcl2 pathway is regulated by miR-204-3p which suppresses the growth of hepatocellular carcinoma tumor endothelial cells [117]

miR-204-3p inhibits the PI3Kγ pathway which usually promotes the release of inflammatory cytokines including IL-12p40 and IL-6

`

-Transfection of macrophages generated from THP-1 cells with pre-miRNA followed by LPS stimulation

-Quantification of inflammatory cytokine production using multiplex cytokine assay

-Targeted genes were identified by overexpressing the miRNA and conducting a cDNA microarray

-miR-204-3p suppression of PI3K-γ was confirmed by luciferase activity assay

Koga et al. (2017) [98]

↑: miR-20a-5p (in homozygous patients) and let-7d-3p and miR-574-3p (in heterozygous patients)

↓: miR-197-3p (in homozygous patients)

Inflammation

The 4 miRNAs, miR-20a-5p, let-7d-3p, miR-574-3p, and miR-197-3p, were shown to be involved in TGF-β, TLR, and NLR signaling pathways, apoptosis, and actin cytoskeleton regulation [91]

miR-197-3p was proved to repress the expression of IL1-R1 resulting in the decrease of IL-1β expression and production in FMF patients

miR-197-3p anti-inflammatory role was validated by:

- pre-miR-197 transfection

-Inflammation related functional assays, apoptosis assay, cell migration assay

-Confirmation via anti-miR-197 transfection

-Targeting genes studied via 3’UTR luciferase activity assay

Akkaya-Ulum et al. (2017,2021)

[91, 101]

In rheumatoid arthritis, miR-20a was reported to have an anti-inflammatory role by regulating the expression of apoptosis signal-regulating kinase (ASK) 1 which is involved in TLR4 pathway particularly upstream of p38 mitogen-activated protein kinase. Additionally, mir-20 a was found to target signal-regulatory protein α (SIRPα) involved in the regulation of leukocyte inflammatory responses [118, 119]

In hepatitis B virus infection, miR-197 was shown to promote liver inflammation by acting on IL-18 [120]

In hepatocellular carcinoma, miR-107 was shown to target the IL-6/STAT3 inflammatory signaling pathway [121]

↓: miR-181a and miR-125a

Inflammation

miR-181a is involved in the differentiation and activation of T cells [110]

N/A

N/A

AbdelKawy et al. (2021) [109]

miR-125a decreases the production of IL-10 receptor α, IL-2 receptor β, and IFN-γ [109]

↓: miR-125a, miR-132, miR-146a, miR-155, miR-15a, miR-16, miR-181a, miR-21, miR-223, miR-26a, and miR-34a

Inflammation

mir-155 plays an anti-inflammatory role by inhibiting molecules including matrix metalloproteinases, protein phosphatase 2A, TLR ligands, and IL-2 [103]

N/A

N/A

Hortu et al. (2019)

[102]

mir-223, mir-16, and mir-15a are shown to decrease inflammation by inhibiting the NF- κB pathway in a similar way to NF-κB kinase inhibitors [104]

miR-132 has an anti-inflammatory role by affecting the TLR4-NFκB-TNF-a/IL-1β signaling pathway [102]

Decrease in mir-125a expression in lupus T cells was associated with an increase in the activity of Kruppel-like factor 13 and an overproduction of the inflammatory chemokine RANTES [122]

↑: miR-4520a

Autophagy

N/A

miR-4520a targets RHEB which activates mTOR pathway

Using in silico and bioinformatic analysis, RHEB was found to be the target of miR-4520a

Latsoudis et al. (2017)

[100]

↑: miR-15a-5p, miR-29b-3p, miR-181a-5p, miR-181b-5p, miR-181c-5p, miR-214-3p, and miR-365a-3p

↓: let-7a-5p, let-7c, let-7 g-5p, miR-15b-5p, miR-16-5p, miR-17-5p, miR-23a-3p, miR-24-3p, miR-25-3p, miR-26a-5p, miR-26b-5p, miR-27a-3p, miR-29c-3p, miR-30a-5p, miR-30d-5p, miR-30e-5p, miR-106b-5p, miR-146a-5p, and miR-195-5p

Apoptosis

miR-181b-5p suppresses apoptosis by affecting MEK/ERK/p21 pathway [108]

N/A

N/A

Karpuzoglu et al. (2020)

[105]

Downregulation of miR-17-5p was shown to promote apoptosis by increasing the expression of phosphatase and tensin homolog while the decrease in miR-25 expression was shown to induce apoptosis by upregulating high mobility group box 1 [123, 124]

Upregulation of miR-16-5p and miR-195-5p were reported to activate caspases 3 and 9 [106, 107]