Table 2.
Lists the function of miRNAs in the course of sepsis.
| miRNA | Pattern of Expression | Clinical Samples/Animal Model | Assessed Cell Lines | Targets / Regulators | Signaling Pathways | Description | Reference |
|---|---|---|---|---|---|---|---|
| miR-15a-5p | ↑ | GEO database: GSE94717 (6 patients with sepsis-induced AKI and 6 HCs) | MPC5 | ↓ XIST, ↓ CUL3 | _ | Downregulation of miR-15a-5p reduced apoptosis in sepsis-induced AKI. | (65) |
| miR-494-3p | ↓ | _Patients with sepsis and HCs | RAW264.7 | ↑ TLR6 | _ | Upregulation of microRNA-494-3p reduced inflammation, TNF-α level, and prevented nuclear translocation of NF-κB p65. | (132) |
| miR-218 | ↓ | 53 Patients with sepsis and 20 HCs, septic mouse model | PBMCs | ↑ VOPP1 | ↑ JAK/STAT pathway | Upregulation of microRNA-494-3p reduced inflammation. | (133) |
| miR-218 | ↓ | male S SD rats | RAW264.7 | ↑ RUNX2 | Up-regulation of miR-218 inhibited inflammatory response. | (141) | |
| miR-122 | ↑ | 25 patients with sepsis and 25 patients with local wound infections as a control group | _ | _ | _ | miR-122 showed higher AUC in comparison with CRP and TLC which had 66.6% sensitivity, 50% specificity, and 56.0% accuracy as a prognostic biomarker for sepsis. | (134) |
| miR-208a-5p | ↑ | septic mouse model | _ | ↓ SOCS2 | ↑NF-κB/HIF-1α pathway | Downregulation of miR-208a-5p decreased reduced degree of mitochondria swelling, and inhibited apoptosis. | (135) |
| miR-328 | ↑ | 110 Patients with sepsis and 89 HCs, male SD rats | _ | _ | _ | miR-328 expression was positively associated with Scr, WBC, CRP, PTC, APACHE II score, and SOFA score. miR-328 was found to be a good diagnostic value for sepsis. Downregulation of miR-328 reduced inflammatory response. | (139) |
| miR-452 | ↑ | 47 sepsis patients with AKI, 50 patients without AKI, and 10 HCs | BUMPT | NF-KB | _ | Serum and urinary miR-452 could be a potential biomarker for early detection of septic AKI. It was upregulated in sepsis patients with AKI compared with without AKI. miR-452 had high diagnostic value for AKI. | (140) |
| miR‐21 | ↓ | 219 Patients with sepsis and 219 HCs | _ | _ | _ | miR‐21 was found to be a good value in predicting sepsis risk. miR‐21 expression was negatively correlated with APACHE II, SOFA score, and 28‐day mortality risk. | (142) |
| miR‐126 | ↑ | 208 Patients with sepsis and 210 HCs | _ | _ | _ | miR‐126 expression was positively correlated with APACHE II, serum creatinine, CRP, TNF‐α, IL‐6, IL‐8, mortality rate, but negatively with IL‐10. | (143) |
| mir-103 | ↓ | 196 Patients with sepsis and 196 HCs | _ | _ | _ | mir-103 predicted high ARDS risk. Mir-103 and was negatively associated with APACHE II score, SOFA score, serum creatinine, CRP, TNF, IL- 1β, IL-6, IL-8, 28-day deaths, but positively correlated with albumin. | (144) |
| mir-107 | ↓ | 196 Patients with sepsis and 196 HCs | _ | _ | _ | mir-107 predicted high ARDS risk. mir-107 and was negatively associated with APACHE II score, SOFA score, serum creatinine, CRP, TNF, IL- 1β, IL-6, IL-8, 28-day deaths, but positively correlated with albumin | |
| miR-92a | ↑ in sepsis-induced ARDS | 53 sepsis patients (36 patients with sepsis-induced ARDS) | HPMEC, A549 | _ | ↓ Akt/mTOR signaling pathway | Downregulation of mir-92a reduced apoptosis and inflammatory response, and enhanced migration | (145) |
| miR-98 | ↓ | male C57BL/6 mice | _ | ↑ HMGA2 | ↑ NF-κB pathway | Upregulation of miR-98 prevented HMGA2, NF-κB, TNF-α, IL-6, Bcl-2 and augmented IL-10, Cleaved caspase-3 and Bax expression, it reduced LVEDP, CTn-I, BNP, ALT, AST, TBIL, LDH, and PaCO2 but elevated +dp/dt max, -dp/dt max, pH and PaO2. | (146) |
| miR‐125a | ↑ | 150 Patients with sepsis and 150 HCs | _ | _ | _ | miR‐125a expression was positively associated with Scr, APACHE II score, SOFA score. | (147) |
| miR‐125b | ↑ | 150 Patients with sepsis and 150 HCs | _ | _ | _ | miR‐125b was correlated with Scr, CRP, APACHE II score, SOFA score, and chronic obstructive pulmonary disease , and 28-day deaths. | |
| miR-199a | ↑ | male C57BL/6 mice | _ | ↓ SIRT1 | _ | Downregulation of miR-199a reduced apoptosis and inflammatory response. | (148) |
| miR-495 | ↓ | 105 Patients with sepsis and 100 HCs, rats | _ | _ | _ | miR-495 was negatively correlated with Scr, WBC, CRP, PCT, APACHE II score and SOFA score. CLP rats showed worse LVSP, LVEDP, ± dp/dtmax, and exhibited an increase in serum CTn-I, CK-MB, TNF-α, IL-6 and IL-1β. | (149) |
| miR-106a | ↑ | 50 patients with sepsis and 30 HCs, clean Kunming mice | TCMK-1 | ↓ THBS2 | _ | Downregulation of miR-106a reduced apoptosis and inflammatory response. | (150) |
| miR‐146a | _ | male C57BL/6 mice | MSCs | IL‐1β | – | IL‐1β stimulation resulted in packaging miR‐146a into exosomes. The exosomal miR‐146a was transferred to macrophages, yielded to M2 polarization, and finally led to high survival in septic mice. | (151) |
| miR-574 | ↓ | CLP-treated mice | HBE | ↑ C3 | _ | Upregulation of mir-574 increased viability, inhibited apoptosis, and reduced sepsis-induced ERS. | (152) |
| miR-195 | _ | wistar rats with sepsis | _ | TGF-β1/Smads signaling pathway, | MicroRNA-195 could promote cardiac remodeling by up-regulating the nanoantibiotics signaling pathway in sepsis rats. | (153) | |
| miR-133a | ↑ | septic mouse model | RAW264.7 | ↓ SIRT1 | _ | Downregulation of miR-133a prevented inflammatory response, sepsis-induced lung, liver and kidney injuries. | (154) |
| miR-191-5p | ↓ | female Wistar rats | _ | ↑ OXSR1 | ↑ p38 MAPK/NF-κB signaling pathway | Upregulation of miR-191-5p prevented inflammatory response and apoptosis in | (155) |
| miR-146a | ↑ | 180 patients with sepsis and 180 HCs | _ | _ | _ | MiR-146a was of good value in predicting high sepsis risk and 28-day mortality risk. MiR-146a was positively associated with biochemical indices, inflammatory cytokines, overall disease severity. | (156) |
| miR-146b | ↑ | 180 patients with sepsis and 180 HCs | _ | _ | _ | miR-146b was of good value in predicting high sepsis risk and 28-day mortality risk. MiR-146a was positively associated with biochemical indices, inflammatory cytokines, and overall disease severity. . |
|
| miR-126 | ↓ | 20 patients with sepsis and 30 patients with general infection | _ | _ | _ | miR-126 was negatively associated with the levels of caspase-3, APACHE II score, and positively with 28-day cumulative survival rate. AUC for predicting the prognosis by miR-126 was 0.823. | (157) |
| miR-223 | _ | C57BL/6 mice | RAW264.7 | _ | _ | Upregulation of mir-223 impelled M2 macrophage through lower activity of glycolysis Pathway. the Implementation of miR-223 over-expressed macrophages with IL-4 pre-conditioning alleviated sepsis severity. |
(158) |
| miR-146b | ↓ | septic mouse model | HK-2 | ↑ IRAK1 | ↑ NF-κB pathway | Treatment with hucMSC-Ex improved survival in mice with sepsis by reducing levels of IRAK1, increasing of miR-146b level, and inhibition of NF-κB activity. | (159) |
| miR-1-3p | ↑ | male SD rats | HUVECs | ↓ SERP1 | _ | miR-1-3p decreased proliferation, and increased apoptosis, and permeability and HUVECs membrane injury. | (160) |
| miR-25 | ↓ | 70 patients with sepsis and 30 patients with SIRS | _ | _ | _ | Levels of miR-25 was negatively associated with the severity of sepsis, SOFA score, CRP and PCT level, 28-day deaths, and levels of oxidative stress indicators. | (161) |
| miR-370-3p | ↑ in SAE | 12 patients with sepsis without encephalopathy, 17 patients with SAE, 20 patients with severe uremia and 12 HCs , male C57BL/6 mice | _ | _ | _ | miR-370-3p was associated with TNF-α and increased brain apoptosis in SAE mice. | (162) |
| miR-21 | ↑ | GEO database: GSE26440 (88 children with septic shock and 26 HCs), C57BL/6 mice | _ | ↓ A20, ↑ NLRP3 | ↑ NF-κB pathway | Downregulation of miR-21 inhibited inflammasome activation, ASC pyroptosome, LPS-induced pyroptosis and septic shock. | (136) |
| miR-21 | ↓ | CLP mouse model | _ | ↑ PDCD4, ↑ PTEN | PDCD4/NF-κB and PTEN/AKT pathways | rIPC protected kidneys from injury by miR-21. miR-21 was transported from ischemic limbs to the kidneys by exosomes. | (163) |
| miR-21 | ↓ | septic mouse model | MTEC | ↑ PDCD4 | ↑ NF-κB pathway | Upregulation of miR-21 reduced inflammation and apoptosis. | (137) |
| miR-21 | _ | septic mice | _ | _ | _ | Hyperoside decreased miR-21 levels so reduced inflammatory responses and increased viability. | (164) |
| miR-21 | ↓ | _ | MSCs | ↑ PDCD4 | _ | βMSCs-derived exosomes reduced symptoms in septic mice and improved their survival rate through miR-21 upregulation. | (138) |
| miR-21 | ↑ | septic C57BL/6J mice | _ | ↓ PGE2, ↓ IL-10 | _ | Downregulation of miR-21 reduced bacterial growth, systemic inflammation, organ damage, macrophage glycolysis, and increased animal survival. | (165) |
| miR-21-3p | ↑ | SD rats | TECs | ↓ AKT, ↓ CDK2, ↑ FOXO1 | – | miR-21-3p regulated lipid metabolism and increased cell cycle arrest and apoptosis. | (166) |
| miR-34 | ↑ | male C57BL/6 mice (15 control group and 15 sepsis model group) | _ | ↓ KLF4 | _ | Plasma miR-34a was positively associated with SCr and BUN. | (167) |
| miR-483-5p | ↑ | CLP-treated mice | PMVECs | ↓ PIAS1 | _ | Downregulation of miR-483-5p reduced inflammation and apoptosis and improved lung injury in mice with sepsis-induced ALI. | (168) |
| miR-181-5p | ↓ | CLP- treated mice | _ | ↑ HMGB1 | _ | Upregulation of miR-181-5p reduced inflammatory response, and sepsis-induced renal and hepatic dysfunction. | (169) |
| miR-20a | _ | SD rats | _ | _ | _ | miR-20a could deteriorated AKI via activating autophagy in sepsis rats. | (170) |
| hsa-miR-92a-3p | ↓ in sepsis-induced coagulopathy group | 116 patients with sepsis | _ | _ | _ | AUC of hsa-mir-92a-3p was 0.660. Levels of plasma hsa-mir-92a-3p were related to plasma lipocalin-2 level, activated partial thromboplastin time, and prothrombin activity. | (171) |
| miR-93-5p | ↓ | septic mouse model | HK2 | ↑ KDM6B, ↓ H3K27me3 | _ | Extracellular vesicles containing miR-93-5p reduced inflammation, apoptosis, multiple organ injury, and vascular leakage in septic mice. | (172) |
| miR-223 | ↓ | 143 patients with sepsis and 44 HCs | _ | _ | _ | Expression of miR-223 was negatively correlated with SOFA scores and positively with survival rate. Upregulation of miR-223 decreased apoptosis and increased proliferation and G1/S transition. | (173) |
| miR-34a | ↑ | male C57BL/6 mice | _ | ↓ SIRT1, ↓ ATG4B | _ | Downregulation of miR-34a reduced inflammatory response and pyroptosis, apoptosis and enhanced autophagy. | (174) |
| miR-30a | ↑ | septic rats | _ | ↓ SOCS-1 | ↑ JAK/STAT signaling pathway | Upregulation of miR-30a promoted apoptosis and inhibited proliferation. | (175) |
| miR-150-5p | ↓ | rat septic shock model | H9C2 | ↑ Akt2 | _ | Upregulation of miR-150-5p inhibited apoptosis. | (176) |
| miR-140 | ↓ | SPF male BALB/c mice | _ | _ | ↑ WNT signaling pathway | Upregulation of miR-140 inhibited apoptosis and inflammation, skeletal muscle glycolysis and atrophy. |
(177) |
| miR-22-3p | ↓ | male SD rats | HK-2 | ↑ HMGB1, ↑ PTEN | _ | Upregulation of miR-22-3p inhibited apoptosis and inflammatory response | (178) |
| miR-205-5b | ↑ | BALB/c mice | RAW264.7 | HMGB1 | _ | Down regulation of miR-205-5b increased HMGB1 expression in LPS-induced sepsis. | (179) |
| miR-526b | ↓ | BALB/c mice | HK2 | ↑ ATG7 | _ | Upregulation of miR-526b increased viability by inhibiting autophagy. | (180) |
| miR-145a | ↓ | septic mouse model | _ | ↑ Fli-1 | ↑ NF-κB signaling | Upregulation of miR-526b reduced levels of proinflammatory cytokines. | (181) |
| miR‐125a | ↑ | 150 patients with sepsis and 150 HCs | _ | _ | _ | AUC of miR‐125a: 0.749 miR‐125a was positively correlated with APACHE II score and SOFA score. |
(182) |
| miR‐125b | ↑ | 150 patients with sepsis and 150 HCs | _ | _ | _ | AUC of miR‐125b: 0.839 miR‐125b was positively correlated with APACHE II score, SOFA score CRP, TNF‐α, IL‐6, IL‐17, IL‐23, and 28‐day mortality risk. |
|
| miR-122 | ↑ | 108 patients with sepsis and 20 patients with infections without sepsis as controls | _ | _ | _ | AUC of miR-122: 0.760 miR-122 was found as independent prognostic factor for 30-day mortality. |
(183) |
| miR-135a | ↑ | _patients with sepsis and HCs, BALB/c mice | _ | _ | ↑ p38 MAPK/NF-κB pathway | Upregulation of miR-135a exacerbated inflammation and myocardial dysfunction. |
(184) |
| miR-133a | ↓ | _ | TCMK-1 | ↑ BNIP3L | ↑ NF-κB pathway | Upregulation of miR-133a reduced inflammation and apoptosis. | (185) |
| miR-223 | _ | male C57BL/6 mice | _ | _ | _ | In multiple models of experimental sepsis, miR-223 showed the complex role in the pathogenesis of septic kidney injury. | (186) |
| miR-155 | ↑ | 44 patients with severe sepsis, 102 patients with sepsis, and 19 HCs | ↑ | ↑ | ↑ | AUC of miR-155: 0.782 (for predicting 30-day mortality in ALI) | (187) |
| miR-146a | ↑ | 44 patients with severe sepsis, 102 patients with sepsis, and 19 HCs | ↑ | ↑ | ↑ | AUC of miR-146a: 0.733 (for predicting 30-day mortality in ALI), CC genotype of rs2910164 in miR-146a was correlated with worse treatment result. |
|
| miR-194 | ↑ | _ | H9c2 | ↓ Slc7a5 | ↑ Wnt/β-catenin pathway | Upregulation of miR-194 increased apoptosis. |
(188) |
| miR-30a | ↑ | male C57BL/6 mice | RAW 264.7 | ↓ ADAR1, ↓ SOCS3 | _ | Upregulation of ADAR1 (a target of miR-30a) reduced inflammation and organ damage. |
(189) |
| miR-27b | ↓ | male C57BL/6 mice | BMMSCs | ↑ JMJD3 | ↑ NF-κB signaling pathway | Upregulation of miR-27b MSC-derived exosomes reduced pro-inflammatory cytokines. | (190) |
| miR-155 | ↑ | BALB/c mice | _ | ↓ SOCS1 | ↑ JAK/STAT signaling | Downregulation of miR-155 alleviated LPS-induced mortality and liver injury | (191) |
| miR-155 | ↓ | C57BL/6 mice | _ | ↑ Arrb2 | ↑ JNK signaling pathway | Upregulation of miR-155 ameliorated late sepsis survival and its cardiac dysfunction, and reduced pro-inflammatory responses. | (192) |
| miR-155 | ↑ | _patients with sepsis and HCs, mouse septic shock model | _ | ↓ CD47 | _ | Downregulation of microRNA-155 reduced sepsis-associated cardiovascular dysfunction and mortality. | (193) |
| miR-155 | ↑ | 60 patients with sepsis and 20 HCs | _ | ↑ Foxp3 | _ | Expression of miR-155 was correlated with APACHEII score, it was significantly higher in non-survival group. | (194) |
| miR-155 | ↑ in sepsis and ALI/ARDS than sepsis but no ALI/ARDS | 156 patients with sepsis (41 with ALI and 32 with ARDS) | _ | _ | _ | AUC of miR-155: 0.87, miR-155 was positively associated with IL-1β, TNF-α levels, and ALI/ARDS score, but negatively with PaO2/FiO2. |
(195) |
| miR-29c-3p | ↑ | 86 patients with sepsis and 85 HCs, male SD rats | _ | _ | _ | AUC of miR-29c-3p: 0.872 miR-29c-3p expression was positively correlated with APACHE II score, SOFA score, levels of CRP and PCT. miR-29c-3p was found to be an independent factor in the occurrence of cardiac dysfunction. |
(196) |
| miR-125b | ↓ | 40 patients with sepsis and HCs, female and male C57BL/6 mice | _ | ↓ PTEN, ↑ MyD88 | _ | PTEN increased miR125 production through associating with the nuclear localization of Drosha-Dgcr8. Downregulation of PTEN resulted in cytokine production, MyD88 abundance and mortality. |
(197) |
| miR-203b | ↓ | 40 patients with sepsis and HCs, female and male C57BL/6 mice | _ | ↓ PTEN, ↑ MyD88 | _ | PTEN increased miR203b production through associating with the nuclear localization of Drosha-Dgcr8. Downregulation of PTEN resulted in cytokine production, MyD88 abundance and mortality. |
|
| miR-146 | ↓ | _ | EA. hy926 | _ | ↑ NF-κB signaling pathway | Upregulation of reduced levels inflammatory cytokines. | (198) |
| miR-140-5p | ↓ | male SPF rats | MLE-12 | ↑ TLR4, ↑ MyD88 | ↑ NF-κB signaling pathway | Shikonin could alleviated sepsis- induced ALI by increasing the levels of miRA-140-5p and decreasing the levels of TLR4. | (199) |
| miR-125b | ↓ | male C57BL/6 mice | HUVECs | ↑ ICAM-1, ↑ VCAM-1, ↑ TRAF6 | ↑ NF-κB signaling pathway | Upregulation of miR-125b alleviated sepsis-induced cardiac dysfunction and ameliorated survival. |
(200) |
| miR-494 | ↑ | ARDS rat models | _ | _ | ↓ Nrf2 signaling pathway | Upregulation of miR-494 increased inflammatory response, oxidative stress and ALI. | (201) |
| miR-146a | ↓ | male C57BL/6 mice | H9C2, J774 | ↑ IRAK, ↑ TRAF6 |
↑ NF-κB signaling pathway | Upregulation of miR-146 reduced levels of inflammatory cytokines and sepsis-induced cardiac dysfunction | (202) |
| miR-223 | _ | 221 patients with sepsis and 75 HCs, male C57Bl/6 mice | _ | _ | _ | Levels of serum miR-223 did not differ between critically ill patients and HCs, but ICU patients with APACHE-II score had moderately decreased circulating miR-223. | (203) |
| miR-300 | ↓ | septic mouse model | _ | ↑ NAMPT | ↓ AMPK/mTOR signaling pathway | Upregulation of miR-300 increased autophagy, cell cycle entry and reduced apoptosis and inflammatory response. | (204) |
| miR-126 | ↓ | male C57BL/6 mice | _ | ↓ HSPA12B | _ | Upregulation of HSPA12B increased levels of miR-126, upregulation of miR-126 reduced levels of dhesion molecules and improved sepsis–induced cardiac dysfunction. | (205) |
| miR-10a | ↓ | 62 patients with sepsis and 20 HCs | _ | ↑ MAP3K7 | ↑ NF-κB pathway | miR-10a expression was negatively association with disease severity scores, levels of c-reactive protein, procalcitonin, and 28-day death. | (206) |
| miR-146a | ↓ | mice | _ | ↑ Notch1 | ↑ NF-κB signaling | Upregulation of miR-146a reduced inflammatory responses of macrophages and protected mice from organ damage | (207) |
| miR-19a | ↓ | CLP mice | RAW 264.7 | ↑ Fn14 | _ | Upregulation of miR-19a reduced LPS-Induced Tubular Damage, it was found to protected mice from sepsis-induced AKI. | (208) |
| miR-214 | _ | male Kunming mice | _ | _ | _ | Upregulation of miR-214 reduced apoptosis, inflammatory response, myocardial injury, and improved cardiac function in SIMI. | (209) |
| miR-539-5p | ↓ | male C57BL/6 mice | MPVECs | ↑ ROCK1 | _ | Upregulation of miR-539-5p reduced apoptosis, inflammatory response, sepsis-induced pulmonary injury. | (210) |
| miR-155 | ↑ | 60 patients with sepsis and 30 HCs | _ | _ | _ | miR-155 was positively correlated with a higher SOFA score and a greater severity. AUC of miR-155 for 28-day survival was 0.763. miR-155 derived immunosuppression through CD39(+) Tregs. | (211) |
| miR-146a | ↑ in sepsis group compared to shame group | male BALB/C mice | _ | _ | _ | Up-regulation of miR-146a reduced levels of inflammatory cytokine TNF-α and mitigated inflammatory reaction and lung tissue injury in sepsis-induced ALI. | (212) |
| miR-7110-5p | ↑ | 52 patients with pneumonia, 44 patients with sepsis and 21 HCs | _ | _ | _ | The sensitivity and specificity of miR-7110-5p were 84.2 and 90.5% respectively. (sepsis vs HCs) | (213) |
| miR-223-3p | ↑ | 52 patients with pneumonia, 44 patients with sepsis and 21 HCs | _ | _ | _ | The sensitivity and specificity of miR-223-3p were 82.9 and 100% respectively. (sepsis vs HCs) | |
| miR-19a | ↑ | patients with sepsis | B cells from patients with sepsis | CD22 | _ | Expression of CD22 initially increased but subsequently reduced. Upregulation of miR-19a resulted in an increased BCR signaling, while overexpression of CD22 reduced the effect of miR-19a and promoted its expression. | (214) |
| miR-206 | ↑ | 63 patients with sepsis, 30 patients with septic shock and HCs | _ | _ | _ | miR-206 was positively associated with SOFA sore and APACHE-II score. It was observed an activated partial thromboplastin time and notably longer prothrombin time. | (215) |
| miR-146a | ↓ | male C57BL/6 mice | RAW264.7 | _ | ↑ NF-κB signaling | Up-regulation of miR-146a reduced apoptosis, inflammatory response, and weakened organ injury in splenic macrophages. | (216) |
| miR-19b-3p | ↓ | 103 patients with sepsis and 98 HCs | HUVECs | _ | _ | Up-regulation of miR-19b-3p reduced inflammatory response. miR-19b-3p was found to be an independent prognostic factor for 28-day survival. | (217) |
| miR-129-5p | ↓ | CLP mice | MLE-12 | ↑ HMGB1 | _ | Up-regulation of miR-129-5p reduced apoptosis, inflammatory response, , lung wet/dry weight ratio, and myeloperoxidase activity. | (218) |
| miR-23b | ↓ | 30 patients with sepsis and 30 HCs | THP-1 | ↑ ADAM10 | _ | Up-regulation of miR-23b reduced apoptosis and inflammatory response. | (219) |
| miR-150 | ↓ | 140 patients multiple trauma and 10 HCs | MDSCs | ↑ ARG1 | _ | Up-regulation of miR-150 reduced IL-6, TGF-β and IL-10. | (220) |
| miR-375 | ↓ | _ patients with sepsis, septic mice | MDSCs | ↑ miR-21 | ↑ JAK2/STAT3 pathway | Up-regulation of miR-375 reduced the number of sepsis Gr1+CD11b+ MDSCs in mice. | (221) |
| miR-31 | ↑ | male SD rats | CACO-2 | ↓ HMOX1 | ↑ NF-κB/HIF-1α pathway | Downregulation of miR-31 reduced intestinal barrier function, intestinal mucosal permeability, oxidative damage and inflammation level. | (222) |
| miR-21 and miR-181b | ↑ (in early sepsis) sustained (in late sepsis) | male BALB/c mice | MDSCs | ↑ NFI-A | _ | Down regulation of miR-21 and miR-181b decreased, immunosuppression, reprograming myeloid cells, late-sepsis mortality, and improved bacterial clearance. | (223) |
| miR-150 | ↓ slightly | 223 critically ill patients (including 138 fulfilled sepsis criteria) and 76 HCs | _ | _ | _ | serum levels of miR-150 were associated with hepatic or renal dysfunction. Low levels were correlated with an unfavorable prognosis of patients. serum levels of miR-150 were not suitable for predicting of sepsis. | (224) |
| miR-10a | ↑ | SD rats | _ | _ | ↑ TGF-β1/Smad pathway | Up-regulation of miR-10a increased ROS, TNF-α, IL-6, and MPO, and downregulation reduced sepsis-induced liver injury. | (225) |
| miR-145 | ↓ | septic mice | HUVECs | ↑ TGFBR2, ↑ SMAD2, ↑ DNMT1 | _ | Up-regulation of miR-145 reduced LPS-induced sepsis and improved the overall survival of septic mice. | (226) |
| miR-150 | ↓ | 17 patients with sepsis and 32 HCs | _ | _ | _ | Levels of miR-150 were negatively correlated with the level of disease severity, TNF-α, IL-10, and IL-18. | (227) |
| miR‐103a‐3p | ↑ | 30 patients with sepsis and 30 HCs, male C57 BL/6 mice | AML12, LO2 | ↓ FBXW7 | _ | Downregulation of miR‐103a‐3p reduced apoptosis, and inflammatory response. | (228) |
| miR-143 | ↑ | 103 patients with sepsis, 95 patients with SIRS and 16 HCs | _ | _ | _ | miR-143 was positively correlated with SOFA score and APACHE II score in patients with sepsis. For distinguishing between sepsis and SIRS, miR-143 showed a sensitivity of 78.6% and specificity of 91.6%. | (229) |
| miR-145 | ↓ | 33 patients with sepsis and 22 HCs, septic mice | BEAS-2B | ↑ TGFBR2 | _ | Up-regulation of miR-145 reduced inflammatory response and improved the overall survival of septic mice. | (230) |
| miR-150 | ↓ | C57Blk/6J mice | HPAECs | ↑ Ang2 | _ | Downregulation of miR-150 damaged adherens junctions reannealing after injury, which caused an irreversible increase in vascular permeability. Up-regulation of miR-150 reduced vascular injury and mortality. | (231) |
| miR-34b-3p | ↓ | CLP mice | RMCs | ↑ UBL4A | ↑ NF-κB signaling | Up-regulation of MiR-34b-3p reduced inflammatory response and AKI in sepsis mice | (232) |
| miR-21-3p | ↑ | _patients with sepsis, C57BL/6 mice | _ | ↓ SORBS2 | _ | Downregulation of miR-21-3p induced mitochondria ultrastructural damage and autophagy in LPS-treated mice. Levels of miR-21-3p increased in patients with cardiac dysfunction than without cardiac dysfunction. | (233) |
| miR-199a-5p | ↑ | C57BL/6 mice | HEK-293T | ↓ SP-D | ↑ NF-κB signaling | Down regulation of miR-199a-5p reduced D-lactic acid, DAO, FD-40, oxidative damage and inflammation. | (234) |
| miR-17 | ↓ | mice | BMSCs, RAW264.7 | ↑ BDR4, ↑ EZH2, ↑ TRAIL | _ | MiR-17 carried by BMSC-EVs reduced inflammation and apoptosis. | (235) |
| miR-125b | ↑ | 120 patients with sepsis and 120 HCs | _ | _ | _ | AUC of miR-125b: 0.658 MiR-125b was positively associated with APACHE II score, SOFA score, Scr, CRP, PCT, TNF-α, and IL-6 levels. miR-125b Was found to be an independent risk factor for mortality risk. |
(236) |
| miR-30e | ↓ | septic rats | _ | ↑ FOSL2 | ↑ JAK/STAT signaling | Up-regulation of miR-30e increased proliferation and reduced apoptosis. | (237) |
| miR-20b-5p | ↑ | SD rats | HEK-293T | ↓ circDMNT3B | _ | Downregulation of miR-20b-5p reduced level of d-lactic acid, FD-40, MDA, diamine oxidase, IL-10, IL-6, oxidative damage and inflammatory factors level. | (238) |
| miR-146b | ↓ | CLP mice | _ | ↑ Notch1 | _ | Up-regulation of miR-146b reduced apoptosis and inflammatory response. | (239) |
| miR-25 | ↓ | SD rats | H9C2 | ↑ PTEN, ↑ TLR4 | ↑ NF-κB signaling | Up-regulation of miR-25 reduced apoptosis and enhanced survival rate. | (240) |
| miR-21 and miR-181b |
↑ | septic mice | MDSCs, Gr1+CD11b + cells |
↑ C/EBPβ, ↑ Stat3 | _ | Stat3 and C/EBPβ increased miR-21 and miR-181b expression by binding to their promoters during sepsis. | (241) |
| miR-17-5p | ↓ | septic mice | LPS-induced macrophages | ↑ TLR4 | _ | Sch B increased miR-17-5p expression and reduced inflammation. | (242) |
| miR-200a-3p | ↑ | male C57BL/6J mice | HBMECs | ↑ NLRP3, ↓ Keap1, ↓ Nrf2, ↓ HO-1 |
_ | Up-regulation of miR-200a-3p induced inflammatory response in sepsis-induced brain injury. | (243) |
| miR-26b | ↓ | 14 patients with sepsis and 7 patients with septic shock and 21 HCs | MEG-01 | ↑ SELP, ↓ Dicer1 | _ | Low levels of miR-26b was correlated with the severity and mortality of sepsis. | (244) |
| miR-96-5p | ↓ | _ | RAW264.7 | ↑ NAMPT | ↑ NF-κB pathway | Up-regulation of miR-96-5p reduced inflammatory response. | (245) |
| miR-27a | ↑ | septic mice | _ | _ | ↑ NF-κB pathway | Downregulation of miR-27a reduced inflammatory response and promoted survival of septic mice. | (246) |
| miR-21a-3p | ↑ | specific pathogen-free SD rats | NRK52E | ↑ Ago2, ↑ Nrp-1 | _ | miR-21a-3p was found to be internalized by TECs via Nrp-1 and Ago2. | (247) |
| miR-574-5p | ↑ | 118 patients with sepsis | _ | _ | _ | miR-574-5p was associated with the death of sepsis patients. | (248) |
| miR-181b | ↓ | 26 patients with sepsis, 36 patients with sepsis plus sepsis/ARDS and 16 HCs, male C57BL/6 mice | THP-1, HUVECs | ↑ importin-α3 | ↑ NF-κB signaling pathway | Up-regulation of miR-181b reduced mortality rate, inflammation response, LPS-induced EC activation, leukocyte accumulation. | (249) |
| miR-182-5p | ↑ | pneumonia mice models | _ | _ | _ | Downregulation of miR-182-5p reduced apoptosis, inflammation response and promoted viability and proliferation. | (250) |
| miR-195 | ↑ | C57BL/6 mice | endothelial cells | ↓ BCL-2, ↓ Sirt1, ↓ Pim-1 | _ | Downregulation of miR-182-5p reduced apoptosis, and improved survival. | (251) |
| miR-205 | ↓ | male SD rats | _ | _ | ↑ HMGB1-PTEN signaling pathway | Up-regulation of miR-205 reduced apoptosis and renal injury. | (252) |
| miR-21-3p | ↑ in AKI group | 49 patients with sepsis-induced AKI and 93 sepsis patients with non-AKI | _ | ↑ Scr, ↑ Cys-C, ↑ KIM-1 |
_ | Levels of miR-21-3p was positively associated with Scr, Cys-C, and KIM-1 in the AKI group. | (253) |
| miR-181a-2-3p | ↓ | GSE46955 data set, CLP mouse model | TCMK-1 | ↑ GJB2 | _ | Up-regulation of miR-181a-2-3p reduced apoptosis and inflammatory response. | (254) |
| miR-21 | ↓ | female Wistar rats | HK-2 | ↑ PTEN, ↓ PI3K, ↓ AKT | _ | Up-regulation of miR-21 suppressed apoptosis and kidney injury. | (255) |
| miR-146a | ↓ | female ICR mice | Raw264.7 | ↑ JMJD3, NF-κB p65 | _ | GSKJ4 reduced inflammatory response by increasing miR-146a levels. Transcription of miR-146a was negatively regulated by JMJD3 through epigenetic mechanism. |
(256) |
| miR-294 | _ | _ | RAW264.7 | TREM-1 | _ | miR-294 reduced TNF-α and IL-6 secretion. | (257) |
| miR-128-3p | ↑ | CLP mouse model | TCMK-1 | ↓ NRP1 | _ | Up-regulation of miR-128-3p promoted apoptosis and inflammatory response and reduced viability. | (258) |
| miR-146a | ↓ | _ | H9C2 | ↓ ErbB4, ↑ TRAF6, ↑ IRAK1 |
_ | Up-regulation of miR-146a reduced apoptosis and inflammatory response and promoted viability. | (259) |
| miR-511 | ↑ in S mice | C57BL/6J (B) mice, SPRET/Ei (S) mice, | _ | Low protein expression of TNFR1 in S mice | _ | miR-511 was induced by glucocorticoids. miR-511 inhibited endotoxemia and experimental hepatitis. | (260) |
| miR-376b | ↓ in sepsis with AKI group | 20 Patients with sepsis with AKI, 20 patients with sepsis without AKI and 10 HCs, male C57BL/6 mice | BUMPT | NF-κB, NFKBIZ | _ | miR-376b inhibited NF-κB inhibitor ζ (NFKBIZ) expression and NF-κB inhibited miR-376b expression so they created a negative feedback loop. | (261) |
| miR-155 | ↑ | female BALB/c mice | _ | _ | _ | DXM treatment suppressed the expression of miRNA-155. |
(262) |
| miR-133a | ↑ | 223 patients with sepsis and 76 HCs, C57Bl/6 mice | _ | _ | _ | High levels of miR-133a was correlated with disease severity, inflammatory response, bacterial infection, and organ failure and predicted an unfavorable outcome of patients. | (263) |
| miR-203 | ↓ | clean grade Kunming mice | HEK-293T | ↑ VNN1 | ↓ AKT signaling pathway | Up-regulation of miR-203 reduced apoptosis, inflammatory response, MDA, ALT, and AST in lung tissues, PMN and PAM levels in BALF and increased SOD activity. | (264) |
| miR-223 | ↑ | 187 patients with sepsis and 186 HCs | _ | _ | _ | AUC for miR-223: 0.754, Plasma miR-223 was associated with disease severity and inflammatory factor levels. miR-223 was found to predict sepsis risk independently. |
(265) |
| miR-146a | ↓ | patients with sepsis and HCs | Human primary T cells | ↑ PRKCϵ | _ | Reduced levels of miR-146a contributes to the pathogenesis of sepsis. | (266) |
| miR-146-a | ↓ | 55 patients with sepsis and 60 HCs | _ | _ | _ | AUC for miR-146-a: 0.803 Serum levels of miR-146-a was negatively correlated with C-reactive protein, pro-calcitonin, IL-6 and TNF-α. |
(267) |
| miR-34a | ↑ | CLP-induced suckling rats | U937 | _ | ↑ STAT3 pathway | Up-regulation of miR-34a promoted iNOS secretion from pulmonary macrophages. | (268) |
| hsa-miR-346 | ↓ | _ | RAW264.7 | ↑ lncRNA MALAT1, ↑ SMAD3 | _ | Up-regulation of hsa-miR-346 promoted proliferation. | (269) |
| miR-214 | ↓ | male Kunming mice | _ | ↑ PTEN | ↓ AKT/mTOR pathway | Up-regulation of miR-214 reduced oxidative stress and autophagy, so ameliorated CLP-induced AKI. | (270) |
| miR-27a | ↑ | LPS induced sepsis mice model | H9C2 | ↓ rhTNFR:Fc, ↓ Nrf2 | _ | rhTNFR:Fc elevated viability and reduced apoptosis by increasing Nrf2 levels and reducing miR-27a levels. | (271) |
| miR-150 | ↓ in non-survival group | 48 patients with septic shock (23 survival patients and 25 non-survival patients) | _ | _ | _ | MiR-150 level was positively associated with cardiac index and negatively with EVLWI and PVPI. | (272) |
| miR-148a-3p | ↑ | male adult wild-type mice and myeloid-specific RBP-J-deficient mice | RAW264.7 | _ | Notch signaling and NF-κB pathway | Up-regulation of miR-148a-3p increased proinflammatory cytokines and decreased protective effect of EVs in LPS induced sepsis. | (273) |
| miR-218-5p | ↑ | male ICR mice | GMCs | ↓ HO-1 | _ | miR-218-5p was reduced in honokiol-treated septic mice, so the survival rate was increased. | (274) |
| miR-425-5p | ↓ | C57BL/6 mice | hepatocytes | ↑ RIP1 | _ | Up-regulation of miR-425-5p reduced inflammatory response and sepsis-related liver damage. | (275) |
| miR-122 | ↑ in CA group | 168 patients with sepsis (CA group and CN group) | _ | _ | _ | Serum levels of miR-122 were associated with APTT ratios, FIB and antithrombin III levels. | (275) |
| miR-101-3p | ↑ | 27 patients with SIC and 15 HCs, male SD rats | H9C2 | ↓ DUSP1 | ↑ MAPK p38 and NF-κB pathways. | Downregulation of reduced apoptosis and inflammatory response. | (276) |
| miR-124 | ↓ | mouse model of ALI | _ | ↑ MAPK14 | ↑ MAPK signaling pathway | Up-regulation of miR-124 reduced apoptosis and inflammatory response and promoted proliferation. | (277) |
| miR-942-5p | ↓ | _ | HK-2 | ↑ FOXO3 | _ | Up-regulation of miR-942-5p reduced apoptosis and inflammatory response and promoted viability. | (278) |
| miR-23a-5p | ↑ | SD rats | NR8383 | _ | _ | _ | (279) |
| miR-1298-5p | ↑ | _ | BEAS-2B | ↓ SOCS6, ↑ STAT3 |
_ | Up-regulation of miR-1298-5p induced cell permeability and inflammatory response and reduced proliferation. | (280) |
| miR-290-5p | ↓ | male C57BL/6J mice | MPC5 | ↑ CCL-2 | _ | Propofol increased levels of miR-290-5p and decreased CCL-2 and inflammatory response. | (281) |
| miR-146a | ↓ | C57BL/6 mice | BMDMs | _ | _ | Rg6 increased IL-10 and miR-146a levels so inhibited inflammatory responses. | (282) |
| miR-223 | _ | C57BL/6 mice | MSCs | Sema3A, Stat3 | _ | WT-exosomes encased high miR-223 levels induced cardio-protection in sepsis. | (283) |
| miR-608 | _ | _ | U937, HEK293T | ELANE | _ | miR-608 played an important role in posttranscriptional regulation of ELANE expression and upregulation of miR-608 reduced inflammation. | (284) |
| miR-124 | ↓ | BALB/c and C57BL/6 mice | RAW264.7 | ↓ α7nAChR, ↑ STAT3 | _ | miR-124 was found to be a critical mediator for the cholinergic anti-inflammatory effect. | (285) |
| miR-26b | ↑ in AKI group | 155 patients with sepsis (68 AKI and 87 non-AKI ) and 57 patients with non-infectious SIRS | _ | _ | _ | Urinary miR-26b levels showed an elevated mortality rate and was correlated with the severity of the disease. | (286) |
| miR-146a | _ | Rat model of SAKI | _ | _ | _ | DEX pretreatment could increase the expression level of miR-146a and reduce oxidative stress and inflammatory responses. | (287) |
| miR-29a | ↑ in AKI group | 74 patients with AKI and 41 without AKI | _ | _ | _ | AUC for miR-29a: 0.82 miR-29a was found to be an independent risk factor for mortality in the septic patients. |
(288) |
| miR-10a-5p | ↑ in AKI group | 74 patients with AKI and 41 without AKI | _ | _ | _ | AUC for miR-10a-5p: 0.75 miR-10a-5p was found to be an independent risk factor for mortality in the septic patients. |
|
| miR-155 | ↑ | septic mice | NCM460 | _ | ↑ NF-κB signaling | Up-regulation of miR-155 increased hyperpermeability to FITC-dextran, TNF-α and IL-6 levels, and decreased ZO-1 and Occludin expression. | (289) |
| miR-155 | ↑ | male C57BL/6 mice | Raw264.7, THP-1 | _ | ↑ PI3K/AKT signalling pathways | Curcumin inhibited inflammatory responses and miR-155 expression. | (290) |
| miR-497 | ↑ in myocardial injury group | 148 patients with sepsis (58 myocardial injury group and 90 non-myocardial injury group) | _ | _ | _ | Plasma miRNA-497 was correlated with cTnI in patients with myocardial injury. | (291) |
| miR-497-5p | ↑ | GEO database, male C57BL/6 mice | BEAS-2B | ↓ IL2RB | _ | Downregulation of miR-497-5p reduced apoptosis and inflammatory responses. | (292) |
| miR-30a | ↓ | _ | monocytes | ↑ STAT1, ↑ MD-2 | _ | miR-30a could inhibit STAT1-MD-2 in monocytes of sepsis. | (293) |
| miR-150 | ↓ | C57BL/6 mice | HUVECs | ↑ NF-κB1 | _ | miR-150 increased survival in patients and inhibited apoptosis and inflammatory responses. | (294) |
| miR-146a | _ | _ | THP-1 | RBM4, Ago2, p38 | _ | Up-regulation of miR-146a inhibited p38 activation and increased Ago2-RBM4 protein interaction, so reduced inflammatory responses. | (295) |
| miR-146a | _ | C57BL/6 mice | HEK293TN, J774.1 | _ | _ | Up-regulation of miR-146a reduced morphine mediated hyper-inflammation. | (296) |
| miR-27a | ↓ | septic mice | _ | ↑ TAB3 | ↑ NF-κB signaling pathway | Paclitaxel pretreatment increased miR-27a levels, so decreased inflammatory responses. | (297) |
| miR-146a | ↓ in septic patients than SIRS and HCs groups | 50 patients with sepsis, 30 patients with SIRS and 20 HCs | _ | _ | _ | AUC for miR-146a: 0.858 | (298) |
| miR-223 | ↓ in septic patients than SIRS and HCs groups | 50 patients with sepsis, 30 patients with SIRS and 20 HCs | _ | _ | _ | AUC for miR-223: 0.804 | |
| miR-339-5p | ↓ | septic mice | RAW264.7 | ↑ HMGB1, ↑ IKK-β | _ | Paeonol could reduce inflammatory responses by upregulating miR-339-5p expression. | (299) |
| miR-99b | ↑ | male C57BL/6 J mice | RAW264.7 | ↓ MFG-E8 | _ | Spherical nucleic acid increased migration by inhibiting miR-99b. | (300) |
| miR-215-5p | ↓ | _ | H9c2 | ↑ LRRFIP1, ↑ ILF3 | _ | miR-215-5p reduced inflammatory responses. | (301) |
| miR-15a | ↑ in sepsis and SIRS than HCs | 166 patients with sepsis, 32 patients with SIRS, and 24 HCs | _ | _ | _ | miR-15a could distinguish sepsis/SIRS from HCs. | (302) |
| miR-16 | ↑ in sepsis and SIRS than HCs | 166 patients with sepsis, 32 patients with SIRS, and 24 HCs | _ | _ | _ | miR-16 could distinguish sepsis/SIRS from HCs. |
miRNAs and Sepsis. AKI, Acute kidney injury; HCs, healthy controls; AUC, significant higher area under curve; CRP, C-reactive protein; TLC, total leucocytes count; SD, Sprague-Dawley; SOFA, sequential organ failure assessment; Scr, serum creatinine; WBC, white blood cell; PCT, procalcitonin; APACHE, physiology and chronic health evaluation; CLP, cecal ligation and puncture; ERS, endoplasmic reticulum stress; AUC, area under the ROC curve; SAE, sepsis-associated encephalopathy; BUN, blood urine nitrogen; rIPC, remote ischemic preconditioning; SPF, specific pathogen-free; GEO, Gene Expression Omnibus; SIMI, sepsis-induced myocardial injury; Tregs, regulatory T-cells; Sch B, Schisandrin B; DXM, dexamethasone; MDA, malondialdehyde; ALT, aminotransferase; AST, aspartate aminotransferase; PAM; pulmonary alveolar macrophages; PMN, polymorphonuclear neutrophils; BALF, bronchoalveolar lavage fluid; SOD, superoxide dismutase; CA, coagulation abnormal; CN, coagulation normal; APTT, serum activated partial thromboplastin time; FIB, fibrinogen; SIC, sepsis-induced cardiomyopathy; SIRS, systemic inflammatory response syndrome; DEX, dexmedetomidine; SAKI, sepsis-induced acute kidney injury).