Novel Insights into the Emerging Role of Neat1 and Its Effects Downstream in the Regulation of Inflammation

Figures & data

Table 1 Preclinical and Clinical Studies Assessing the Effect of NEAT1 on the Regulation of Inflammation in Central Nervous System

Author, Year	Disease’s Type	Diseases Model	Organism	Expression	Identify	Inflammatory Marker	Mechanism	Ref.
Han et al 2019	Stroke	OGD/R	Cells	Up	qRT-PCR	IL-1β, 6, TNF-α	Wnt/β-catenin	[50]
Li et al 2020	Stroke	Patients	Human	Up	qRT-PCR	TNF-α, IL-1β, 6, 8, 10, 17, 22	miR-124, miR-125a	[61]
Ni et al 2020	Stroke	Patients, OGD/R	Human, Cells	Up	qRT-PCR	NA	AKT/STAT3	[62]
Zhang et al 2021	Stroke	MCAO, OGD/R	Rats, Cells	Up	qRT-PCR	IL-1β, 18	miR-22-3p	[59]
Jin et al 2021	Stroke	MCAO	Mice	Up	qRT-PCR	TNF-α, IL-1β, 6, NF-κB	NA	[60]
Ban et al 2020	SCI	LPS treat	Cells	Up	qRT-PCR	IL-1β, 6, 10, TNF-α	miR-29a/BCL2L11	[57]
An et al 2021	SCI	LPS treat	Cells	Up	qRT-PCR	IL-1β, 6, TNF-α	miR-211-5p/MAPK1	[58]
Xie et al 2019	PD	MPP^+ treat	Cells	Up	qRT-PCR	IL-1β, 6, TNF-α	miR-124	[54]
Zhou et al 2020	PD	MPP^+ treat	Cells	Up	qRT-PCR	IL-1β, 6, TNF-α	miR-1277-5p/ARHGAP26	[55]
Liu et al 2020	PD	MPTP, MPP^+ treat	Mice, Cells	Up	qRT-PCR	IL-1β, 6	miR-212-3p/AXIN1	[56]
Liu et al 2020	PD	MPP^+ treat	Cells	Up	qRT-PCR	IL-1β, TNF-α	miR-212- 5p/RAB3IP	[51]
Chen et al 2021	PD	MPP^+ treat	Cells	Up	qRT-PCR	IL-1β, 6, TNF-α	miR-124-3p/PDE4B/mTOR	[52]
Sun et al 2021	PD	MPP^+ treat	Cells	Up	qRT-PCR	IL-1β	miR-1301-3p	[53]
Zhong et al 2017	TBI	OGD/R, ICVI AVV	Mice, Cells	Up	ChIP-qPCR	IL-1, TNF-α	Pidd1	[63]
Wan et al 2020	Epilepsy	Patients, IL-1β treat	Human, Cells	Up	qRT-PCR	IL-1β, 6, TNF-α	miR-129-5p/notch	[64]

Abbreviations: NA, not available; qRT-PCR, quantitative real-time polymerase chain reaction; IL, interleukin; TNF, tumor necrosis factor; OGD/R, oxygen-glucose deprivation/re-oxygenation; MCAO, middle cerebral artery occlusion; AIS, acute ischemic stroke; AKT, protein kinase B; STAT3, signal Transducer And Activator Of Transcription 3; NF-κB, nuclear factor-κB; SCI, spinal cord injury; LPS, lipopolysaccharides; BCL2L11, Bcl-2-like protein 11; MAPK1, mitogen-activated protein kinase 1; PD, Parkinson’s disease; AXIN1, axis inhibition protein 1; MPTP, 1-methyl- 4-phenyl-1, 2, 3, 6-tetrahydropyridine injection; MPP⁺, 1-methyl- 4-phenyl pyridine; RAB3IP, RAB3A-interacting protein; PDE4B, phosphodiesterase 4B; mTOR, mechanistic target of rapamycin; TBI, traumatic brain injury; ICVI, intracerebroventricular injection; AVV, adenovirus; ChIP-qPCR, chromatin immunoprecipitation polymerase chain reaction; Pidd1, p53-induced death domain-containing protein 1.

Table 2 Preclinical and Clinical Studies Assessing the Effect of NEAT1 on the Regulation of Inflammation in Peripheral System

Author, Year	Diseases	Model	Organism	Expression	Identification	Inflammatory	Main Action	Ref.
					Method	Marker	Mechanism
Xia et al 2020	Sepsis	LPS	Mice, Cells	Up	qRT-PCR	TNF-α, IL-6, 10, MCP-1	miR-211/PI3K/AKT	[69]
He et al 2019	Sepsis	Patients	Human	Up	qRT-PCR	TNF-α, IL-1β, 6, 17	miR-124	[71]
Huang et al 2018	Sepsis	Patients	Human	Up	qRT-PCR	CRP, TNF-α, IL-1β, 6, 8, 10	NA	[70]
Chen et al 2019	Sepsis	CLP	Mice	Up	qRT-PCR	TNF-α, IL-1β, 6	miR-125/MCEMP1	[72]
Liu et al 2020	Sepsis	Patients, LPS	Human, Cells	Up	qRT-PCR	TNF-α, IL-1β, 6, 9	miR‐590‐3p	[74]
Wu et al 2020	Sepsis	Patients, LPS	Human, Cells	Up	qRT-PCR	TNF-α, IL-1β, 6, 8	miR-370-3p/TSP-1	[76]
Xiao et al 2020	Sepsis	Patients, LPS	Human, Cells	Up	qRT-PCR	TNF-α, IL-1β, 6, 8	miR-370-3p/Irak2	[77]
Yang et al 2021	Sepsis	LPS	Cells	Up	qRT-PCR	TNF-α, IL-1β, 6	miR-31-5p/POU2F1	[78]
Li et al 2020	Sepsis	Patients, LPS	Human, Cells	Up	qRT-PCR	TNF-α, IL-1β, 6	miR-17-5p/TLR4	[73]
Wang et al 2020	Sepsis	LPS	Cells	Up	qRT-PCR	TNF-α, IL-1β, 4, 6, 10	miR-125a-5p/TRAF6/ TAK1	[75]
Chen et al 2020	MI	As2O3	Cells	Up	qRT-PCR	TNF-α, IL-1β, 6	miR-124/NF-κB	[80]
Gast et al 2019	MI	Patients, LPS	Human, Mice, Cells	Up	RNA-sequencing	TNF-α, IL-6, 10, IFN-γ,	NA	[79]
Wang et al 2019	MI	LPS	Mice	Up	qRT-PCR	TNF-α, IL-1, 6, MCP1	TLR2/NF-κB	[81]
Wei et al 2020	MI	LPS	Cells	Up	qRT-PCR	TNF-α, IL-1β, 6	miR-144-3p	[82]
Liu et al 2019	OA	Patients	Human, Cells	Up	qRT-PCR	TNF-α, IL-1β, 6, 8	miR‐193a‐3p/SOX5	[105]
Wang et al 2019	OA	Patients	Human, Cells	Up	qRT-PCR	TNF-α, IL-1β, 6, 8, COX-2	miR-181a/GPD1L	[106]
Tu et al 2019	OA	Patients, IL-1β	Human, Cells	Up	qRT-PCR	IL-1β	miR-377-3p/ITGA6	[107]
Wang et al 2017	OA	Patients	Human, Cells	Up	qRT-PCR	IL-6, 8	miR-181c	[110]
Huang-Fu et al 2018	AS	ox-LDL	Cells	Up	qRT-PCR	NF-κB	CD36, p65	[83]
Chen et al 2018	AS	ox-LDL	Cells	Up	qRT-PCR	TNF-α, IL-1β, 6	miR-128	[84]
Wang et al 2018	AS	ox-LDL	Cells	Up	qRT-PCR	TNF-α, IL-1β, 6, COX-2	miR‐342‐3p	[85]
Guo et al 2019	AS	Patients, ox-LDL	Human, Cells	Up	qRT-PCR	TNF-α, IL-1β, 6	miR-30c-5p/TCF7	[91]
Feng et al 2020	AKI	Patients, LPS	Human, Cells	Up	qRT-PCR	TNF-α, IL-1β, 6, 8	miR-22-3p	[93]
Gao et al 2020	AKI	Patients, LPS	Human, Cells	Up	qRT-PCR	TNF-α, IL-1β, 6	let-7b-5p/TRAF6	[102]
Wang et al 2020	AKI	Sepsis-induced AKI, LPS	Rats, Cells	Up	qRT-PCR	TNF-α, IL-1β, 6	miR-27a-3p/TAB3	[94]
Wang et al 2018	IBD	Acute colitis	Mice	Up	Bioinformatics	TNF-α, IL-7, 12a, 17a	miR204-5p-PI3K-AKT	[89]
Liu et al 2018	IBD	5% DSS	Mice, Rats, Cells	Up	qRT-PCR	TNF-α, IL-23	Polarization of macrophages	[90]
Pan et al 2021	IBD	Patients, DSS, TNF-α	Human, Mice, Cells	Up	qRT-PCR	IL-8, TNF-α, MCP1	TNFSF1B	[112]
Zhou et al 2020	ALI	Sepsis-evoked ALI, LPS	Mice, Cells	Up	qRT-PCR	TNF-α, IL-1β, 6	HMGB1-RAGE	[86]
Chen et al 2020	ALI	LPS	Mice, Cells	Up	qRT-PCR	TNF-α, IL-1β, 6	miR-944/TRIM37	[101]
Zhang et al 2019	ALI	Patients, LPS	Human, Cells	Up	qRT-PCR	TNF-α, IL-1β, 6	Let-7a/TLR4	[95]
Li et al 2019	Asthma	Patients	Human	Up	qRT-PCR	TNF-α, IL-1β, 6, 17	miR-124	[87]
Wang et al 2021	Asthma	PDGF	Cells	Up	qRT-PCR	IL-4, 6, 13	MiR-9-5p/SLC26A2	[88]
Zhang et al 2016	SLE	Patients, LPS	Human, Cells	Up	qRT-PCR	TNF-α, IL-6	MAPK	[103]
Zhang et al 2019	SLE	LPS	Cells	Up	qRT-PCR	TNF-α, IL-1β, 6, IFN-γ	miR-146b/TRAF6/NF-κB	[104]
Wang et al 2020	RA	Patients, TNF-α	Human, Cells	Up	qRT-PCR	TNF-α	miR-410-3p/YY1	[119]
Rao et al 2021	RA	Bovine type II collagen	Mice, Cells	Up	qRT-PCR	TNF-α, IL-1β, 6	miR-23a/MDM2/SIRT6	[120]
Shao et al 2020	DR	Patients, diabetic animal	Human, Rats, Cells	Up	qRT-PCR	COX-2, TNF-α, IL-6	TGF‐β1, VEGF	[92]
Li et al 2020	Renal fibrosis	UUO, TGF-β1	Mice, Cells	Up	qRT-PCR	IL-1β, 6	miR-129	[111]
Jin et al 2019	NAFLD	Free fatty acid	Cells	Up	qRT-PCR	TNF-α, MCP1, IL-1β, 6	miR-506/GLI3	[96]
Ye et al 2020	ASH	Patients	Human, Mice, Cells	Up	qRT-PCR	TNF-α, IL-1β, 6	miR-129-5p/SOCS2	[97]
Wang et al 2021	ALF	Patients, D-galactosamine	Human, Mice	Up	qRT-PCR	TNF-α, IL-1β, 6	miR-139/PUMA	[98]
Xu et al 2019	ACLF	Patients, LPS	Human, Rats, Cells	Up	qRT-PCR	IL-1, 6, 22	TRAF6	[99]
Zhang et al 2021	NASH	MCD diet	Mice, Cells	Up	qRT-PCR	NF-κB	miR-129-5p/PEG3	[100]
Sun et al 2020	TB	Patients, H37Ra	Human, Cells	Up	qRT-PCR	TNF-α, IL-6, IFN-γ	miR-377–3p	[114]
Sheng et al 2020	AP	Caerulein	Mice, Cells	Up	qRT-PCR	TNF-α, IL-6, 10	miR-216b/MAP2K6	[108]
Zhu et al 2021	CSF	Patients, OGD	Human, Cells	Up	qRT-PCR	TNF-α, IL-6, sICAM-1	miR-148b-3p/ICAM-1	[109]
Wang et al 2018	HCC	Transfection	Cells	Up	qRT-PCR	IL-6	IL-6/STAT3	[113]
Wang et al 2021	I/R	I/R	Cells	Up	qRT-PCR	TNF-α, IL-1β, 6	NA	[115]
Wang et al 2021	AR	Patients	Human	Up	qRT-PCR	IL-4, 6, 10, 17	miR-21, 124, 125a	[116]
Nong et al 2019	Pneumonia	LPS	Cells	Up	qRT-PCR	TNF-α, IL-1β, 6, 8	miR-193a-3p/TLR4/NF-κB	[117]
Dai et al 2021	Bone	LPS	Cells	Up	qRT-PCR	IL-1β, 6	NLRP3 inflammasome	[118]
Zhan et al 2020	DN	STZ, HG	Rats, Cells	Up	qRT-PCR	IL-1β	miR-34c/NLRP3	[121]

Abbreviations: NA, not available; qRT-PCR, quantitative real-time polymerase chain reaction; IL, interleukin; TNF, tumor necrosis factor; PDGF, platelet-derived growth factor; IBD, inflammatory bowel disease; AS, atherosclerosis; MCP-1, monocyte chemoattractant protein-1; DSS, dextran sulfate sodium; HUVECs, human umbilical vein endothelial cells; ox-LDL, oxidized low-density lipoprotein; TCF7, transcription factor 7; UUO, unilateral ureteral obstruction; CRP, C-reactive protein; MCEMP1, mast cell expression membrane protein 1; CLP, cecal ligation and puncture; TSP-1, thrombospondin-1; Irak2, interleukin 1 receptor associated kinase 2; POU2F1, POU domain class 2 transcription factor 1; ALI, acute lung injury; HMGB1, high-mobility group box1; DR, diabetic retinopathy; COX-2, cyclooxygenase‐2; hRECs, human retinal endothelial cells; VEGF, vascular endothelial growth factor; TGF-β1, transforming growth factor-β1; AKI, acute kidney injury; TRAF6, tumor necrosis factor receptor-associated factor 6; TLR4, toll-like receptor 4; NAFLD, non-alcoholic fatty liver disease; ASH, alcoholic steatohepatitis; SOCS2, suppressor of cytokine signaling 2; ALF, acute liver failure; PBMCs, peripheral blood mononuclear cells; PUMA, p53-upregulated modulator of apoptosis; ACLF, acute-on-chronic liver failure; PEG3, paternally expressed gene 3; NASH, non-alcoholic steatohepatitis; MCD diet, methionine choline-deficient diet; NF-κB, nuclear factor-κB; SLE, systemic lupus erythematosus; MAPK, mitogen-activated protein kinase; SLE, systemic lupus erythematosus; IFN-γ, interferon γ; TB, tuberculosis; TRAF6, TRAF6, tumor necrosis factor receptor-associated factor 6; TAK1, transforming growth factor-activated kinase 1; As₂O₃, arsenic trioxide; MI, myocardial infarction or cardiomyocyte injury; OA, osteoarthritis; SOX-5, sex‐determining region Y‐box protein 5; GPD1L, glycerol-3-phosphate dehydrogenase 1-like; AP, acute pancreatitis; CSF, coronary slow flow; sICAM-1, soluble intercellular adhesion molecule-1; TNFSF1B, tumor necrosis factor superfamily member 1B; HCC, hepatocellular carcinoma; STAT3, signal Transducer And Activator Of Transcription 3; I/R, ischemia/reperfusion; AR, allergic rhinitis; NLRP3, Nod‐like receptor protein 3; RA, rheumatoid arthritis; YY1, Yin Yang1; MDM2, murine double minute-2; SIRT6, Sirtuin 6; DN, diabetic nephropathy; NLRP3, Nod-like receptor protein-3; STZ, streptozotocin; HG, high glucose.

Figure 1 The overview of mechanisms of how Neat1 regulates inflammation. (A) In the central nervous system, Neat1 can regulate inflammation and the activation of microglia. (B) In the peripheral system, Neat1 can regulate inflammation and liposome deposition. The completion of all the above effects, mainly through the interaction with various miRNA and mRNA, and thus achieve the regulation of inflammation.

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