Epigenetic Changes and Functions in Pneumoconiosis

Table 1

Main miRNA changes involved in pneumoconiosis.

miRNA	Regulation	Model						Target gene and signal pathway	Reference
		Patients	In vivo		In vitro
			Rat	Mouse	Macrophage	Fibroblast	Alveolar epithelial cell
miR-21/21-5p	Up	√	√	√					[69–72]
miR-96/96-5p	Up	√	√						[68, 73–75]
miR-107-3p	Up	√			RAW264.7			miR-107-3p can inhibit the expression of chordin and its downstream BMP-2, SMAD1/5/9, and ID-1, which is related to the activation of TGF-β signaling pathway.	[76–78]
miR-122-5p	Up	√			RAW264.7				[74–78]
miR-125a-5p	Up	√			RAW264.7	IMR-90		(1) miR-125a directly inhibited the expression of hnRNP K and EZH2; (2) miR-125a-5p can promote the proliferation and apoptosis of NIH/3T3 and promote the occurrence of fibrosis	[68, 74, 75]
miR-132-3p/132-5p/212-3p/212-5p	Up		√						[71]
miR-155/155-3p	Up	√	√						[69, 71]
miR-291a-3p/291b	Up		√						[71]
miR-292-3p/292-5p	Up		√						[71]
miR-293-5p	Up		√			Rat primary lung fibroblasts			[71, 79]
miR-320a/320b/320c	Up	√							[80]
miR-335-5p	Up	√			RAW264.7				[76–78]
miR-466b-2-3p/466b-3p/466b-4-3p/466b-5p	Up		√						[71]
miR-743a-3p/743b-3p/743b-5p	Up		√						[71]
miR-26a/26a-5p/26b	Down		√						[72, 73]
miR-27b-5p	Down	√			RAW264.7				[76–78]
miR-34a-5p/34c-3p/449a	Down	√	√	√		NIH/3T3, MRC-5	A549	miR-34a-5p may play a potential role in inhibiting EMT by inhibiting SMAD4.	[72, 81–84]
miR-99a/99a-5p	Down	√	√						[73, 80]
miR-101/101a	Down		√		NR8383			Overexpressed miRNA-101 in BMSCs can inhibit ATG4D by regulating the endoplasmic reticulum stress of NR8383 cells, and effectively inhibit the autophagy of macrophages caused by silica.	[73, 85–87]
miR-140/140-5p	Down	√	√						[73, 80]
miR-149	Down	√		√			A549, HBE	Overexpressed miR-149 can inhibit the expression of IL-6 in vitro.	[88, 89]
miR-151a-3p	Down	√							[68, 74, 75]
miR-181b	Down		√		NR8383				[73]
miR-222	Down	√							[88, 90]
miR-326	Down			√			A549, HBE	(1) miR-326 inhibited pulmonary inflammation by targeting TNFSF14 in silica-treated lung epithelial cells; (2) miR-326 promoted autophagy activity by targeting PTBP1 in TGF-β–stimulated MRC-5 cells and NIH/3T3 cells models	[91]
miR-370-3p	Down		√			Rat primary lung fibroblasts			[71, 79]
miR-379-3p/379-5p	Down		√						[71]
miR-409-3p/409a-5p	Down	√	√						[68, 71, 73–75]
miR-411-3p/411-5p	Down		√			Rat primary lung fibroblasts		(1) miR-411-3p effectively reduced the progression of silicosis or fibroblast fibrosis by regulating the expression of MRTFA in vivo and in vitro; (2) miR-411-3p could inhibit the expression of SMURF2 and reduce the ubiquitination degradation of SMAD7 regulated by SMURF2, thereby blocking the TGF-β/SMAD signaling pathway and alleviating silicosis pulmonary fibrosis by stimulating the primary lung fibroblasts of rats with TGF-β	[71, 79]
miR-486-5p	Down	√		√		NIH/3T3		miR-486-5p could bind to SMAD2 and participate in the process of pulmonary fibrosis through TGF-β signaling pathway.	[70]
miR-489	Down			√	RAW264.7, THP-1 macrophages	NIH/3T3, MRC-5		(1) miR-489 inhibited the expression of MyD88, IL-1β, and TGF-β in mice and macrophages; (2) miR-489 inhibited total SMAD3 and p-SMAD3 levels and alleviated pulmonary fibrosis in mice and fibroblasts	[92, 93]
miR-503	Down			√			A549, HBE	miR-503 was adsorbed by lncRNA-MALAT1 and downregulated miR-530, increased PI3K and p85, and promoted EMT by regulating the PI3K/AKT/SNAIL signaling pathway.	[94, 95]
miR-542-5p	Down			√		NIH-3T3, MRC-5		Overexpressed miR-542-5p inhibited ITGA6, which in turn inhibited the phosphorylation of FAK/PI3K/AKT and alleviated fibrosis.	[96]
miR-1193-3p	Down		√			Rat primary lung fibroblasts			[71, 79]
Let-7a-3p/let-7a-5p/let-7d/let-7d-3p/let-7d-5p/let-7f/let-7i-5p	Down	√	√			IMR-90	A549	(1) Let-7a-5p has four target genes: BCL2L1, FAS, MAPK8, and IGF1R; (2) The downregulated let-7d in A549 cells can increase the expression of HMGA2 and promote EMT	[68, 73–75, 97]
miR-16/16-2-3p/16-5p	Discord	√							[69, 80]
miR-22/22-5p	Discord	√	√						[73, 80]
miR-25/25-3p	Discord	√	√						[73, 80, 88]
miR-29a/29b/29b-3p/29c	Discord	√	√				A549, RLE-6TN	miR-29b attenuated or even reversed the EMT process induced by silica in vivo and in vitro experiments.	[69, 72, 73, 89, 98]
miR-30a/30c/30c-2-3p/30d/30e	Discord	√	√		RAW264.7				[73, 76–78]
miR-126/126a-5p	Discord	√	√		RAW264.7				[73, 76–78]
miR-146a/146b/146b-3p/146b-5p	Discord	√	√		NR8383				[68, 71, 73–75]
miR-200a-5p/200b/200b-3p/200c/200c-3p	Discord	√	√				A549, Beas-2B	miR-200c was adsorbed by lncRNA-ATB to release ZEB1 and promote the occurrence of EMT.	[89, 98–101]
miR-204	Discord	√	√						[69, 73]
miR-300-3p/300-5p	Discord		√						[71, 73]
miR-423-3p/423-5p	Discord	√	√						[68, 72, 74, 75]