Emerging roles of microRNAs as diagnostics and potential therapeutic interest in type 2 diabetes mellitus

Table 1 MiRNAs involved in type 2 diabetes clinical and pre-clinical evidence

No.	Micro RNA	Status	Disease	Model	Publish year	Ref.
1	miR-96-5p and miR-7-5p		T2DM	Bioinformatic	2022	[31]
2	miR-132	Upregulated	T2DM	Human	2020	[32]
3	hsa-miR-29a-5p	Upregulated	T2DM	Human	2021	[33]
4	miR-143	Upregulated	T2DM	Human	2022	[34]
5	mir-21 and miR-126	Upregulated	T2DM	Human	2022	[35]
6	miR-145-5p, miR-483-3p/5p, miR-138-5p, miR-192-5p, miR-195-5p, miR-320b, and let-7a-5p		T2DM	Human	2019	[36]
7	miR-let-7g-5p	Downregulated	T2DM	Human	2022	[37]
8	miR-187-3p, miR-21-5p, miR-668, miR-199b-5p, mir-216a, miR-25 miR-30a-3p miR-30a-5p		T2DM	Human	2023	[38]
9	miRNA-152-3p	Upregulated	T2DM	Human	2022	[39]
10	Microrna-146a and microrna-130a	Upregulated	T2DM	Human	2019	[40]
11	miR-24-3p	Upregulated	T2DM	Human	2021	[41]
12	miR-126-3p/u6sno	Upregulated	T2DM	Human	2021	[42]

T2DM: Type 2 diabetes mellitus.

Table 2 Role of miRNA in various metabolic pathways

No.	miRNA	Target pathway	Model	Disease	Effect	Ref.
1	miR-21	NF-κβ	db/db mice	Metabolic syndrome and obesity	Up-regulated	[48]
2	miR-124	NF-κβ	Primary rat retinal microglial cells		Down-regulated	[49]
3	miR-471-3p	NF-κβ	Raw264.7 cells and db/db mice	Diabetic cardiomyopathy	Up-regulated	[50]
4	miR-46a	NF-κβ	Human blood	Hyperlipidemia	Up-regulated	[51]
5	miR-200b	NF-κβ	Huvec line		Down-regulated	[52]
6	miR-200c	NF-κβ	Huvec line		Down-regulated	[52]
7	miR-210	PKC			Down-regulated	[54]
8	miR-25	PKC	Adult male balb/c mice and diabetic db/db mice	Diabetic peripheral neuropathy	Down-regulated	[55]
9	miR-21-3p	PKC	Human aortic vsmcs (C-12511, promocell, and human vets	Diabetic atherosclerosis	Down-regulated	[56]
10	miR-92a	PKC	db/db mice	Diabetes mellitus	Up-regulated	[57]
11	miR-185	NO	Three-month-old male sprague–dawley rats	Diabetes mellitus	Down-regulated	[59]
12	miR-195	NO	Mvec cell lines	Deep vein thrombosis	Down-regulated	[60]
13	miR-582	NO	Mvec cell lines	Deep vein thrombosis	Down-regulated	[60]
14	miR-191	PI3K/AKT	Male C57bl/6j mice		Up-regulated	[62]
15	miR-29b-3p	PI3K/AKT	Human serum and Hek-293t cells	Diabetic retinopathy	Up-regulated	[62]
16	miR-29c-3p	PI3K/AKT	Rat	Diabetes mellitus	Up-regulated	[62]
17	miR-199a-5p	PI3K/AKT	Rat	Diabetes mellitus	Down-regulated	[62]
18	miR-532-3p	PI3K/AKT	Rat	Diabetes mellitus	Down-regulated	[62]
19	miR-93-5p	PI3K/AKT	Rat	Diabetes mellitus	Down-regulated	[62]
20	miR-150-5p	PI3K/AKT	Rat	Diabetes mellitus	Down-regulated	[63]
21	miR-345-3p	PI3K/AKT	Rat	Diabetes mellitus	Down-regulated	[64]
22	miR-25-3p	PI3K/AKT	Human blood	Diabetic retinopathy	Down-regulated	[65]
23	miR-214	PI3K/AKT	Male sprague dawley rats	Diabetic nephropathys	Down-regulated	[66]
24	miR-203	PI3K/AKT	Rat	Diabetic foot ulcer	Up-regulated	[67]
25	miR-129-5p	PI3K/AKT	Sprague dawley rats	Intracerebral Haemorrhage	Down-regulated	[68]
26	miR-146b-3p	PI3K/AKT	Human blood		Down-regulated	[69]

PI3K: Phosphoinositide 3-kinase; NF-κβ: Nuclear factor kappa B subunit 1.

Table 3 miRNAs expression in metabolic disease and reported therapeutic approaches

No.	miRNA	Model	Method	Disease	Target	Ref.
1	miR-210	H9c2 cells (rat embryonic cardiac myoblast; ATCC)	miR-210 mimic and inhibitor	Diabetic cardiomyopathy	c-Jun N-terminal kinase (JNK)	[54]
2	miR-29b	db/db mice	Ultrasound-microbubble–mediated gene transfer technique was used to deliver doxycline (Dox)-inducible pre-miR-29b	Diabetic nephropathy	TGF-β/Smad3	[71]
3	miR-146a	HaCaT cells	Mimic and inhibitor miR-146a deliver via lipofecter liposomal transfection	Diabetic foot ulcer	AKAP12, Wnt3a and β-catenin	[72]
4	miRNA-339	Endothelial progenitor cell of humans	Transfection with miRNA-339-5p mimic or miRNA-339-5p inhibitor	Polycystic ovary syndrome	PI3K, AKT and SIRT1 PGC-1α	[73]
5	miR-21	C6 glioblastoma cells	Antagomir-21/RAP nanoparticles	Intracranial glioblastoma	PTEN and PDCD4	[74]
6	miR-107 and miR-103	C57BL/6J	Antagomir of miR-103 and miR-107 delivered by liver-targeting lipid nanoparticle	Diabetes	Caveolin-1	[75]
7	miR-181a	Mouse neuroblastoma cells (Neuro2A) and HEK293T cells and male sprague dawley rats	AMO181a-chol loaded exosomes	Cerebral ischemia	Hypoxia-induced RAGE and Bcl2	[76]

RAGE: Receptor of advanced glycation end products; TGF: Tumor growth factor.