Effect of metformin on the long non-coding RNA expression levels in type 2 diabetes: an in vitro and clinical trial study

The anti-diabetic effects of metformin are mediated by regulating long non-coding RNA

“…For example, growth arrest-specific 5 (GAS5) overexpression suppressed NLRP3 inflammasome activation-mediated pyroptosis by regulating the miR-34b-3p/AHR axis in diabetic cardiomyocytes ( Xu et al, 2020a ). Although there is no direct evidence showing that metformin could regulate NLRP3 by regulating GAS5, clinical trials showed that taking metformin for 2 months was shown to increase GAS5 in patients with T2D ( Parvar et al, 2023 ), indicating its anti-inflammatory role in the diabetic heart. Furthermore, metformin significantly alleviated NLRP3 and GSDMD expressions in diabetic periodontitis mice with a severe inflammation state, and in this study, lncRNA_1810058I24Rik, lncRNA_Gm12474, and lncRNA_Gm41514 were found to be co-expressed with NLRP3 and GSDMD ( Zhou et al, 2020 ), which may potentially be regulated by metformin.…”

“…LncRNAs regulated by metformin potentially affect mitochondrial function; clinical research on DNA methylation in plasma from metformin-treated patients with T2DM showed that 57 lncRNA-associated DNA methylation regions were found, which included the mitochondrial ATP synthase-coupling factor 6 (ATP5J) ( Solomon et al, 2020 ), suggesting that metformin may regulate ATP5J through lncRNAs. In addition, metformin increases GAS5 expression in HepG2 cells and the plasma of patients with T2DM ( Parvar et al, 2023 ), and elevated GAS5 decreases mitochondrial tricarboxylic acid flux by disrupting the metabolic enzyme tandem of the tricarboxylic acid cycle ( Sang et al, 2021 ), providing another explanation for the mitochondrial inhibition effects of metformin. Moreover, metformin decreases the expression of H19, while H19 has been shown to downregulate the expression of Mfn-2, a key protein for mitochondrial fusion, in type 1 diabetic renal tissues ( Sultan et al, 2021 ), and a decline in Mfn2 was observed in both type 1 and type 2 diabetic rodents ( Gao et al, 2012 ; Veeranki et al, 2016 ), suggesting that metformin may regulate Mfn2 by decreasing H19.…”

The emerging role of MALAT1 lncRNA in diabetic nephropathy: based on the review of the literature and bioinformatic analysis

“…Promising evidence has revealed that lncRNAs could serve as potential biomarkers for early diagnosis of diabetes and its complications (17,37). In this regard, it has been demonstrated that MALAT1 is significantly upregulated in DN tissues compared with normal (57).…”

“…In recent years, there has been an uptick in the amount of evidence suggesting that noncoding RNA (ncRNA), in particular long noncoding RNAs (lncRNAs), play an important part in the development and progression of DN (12)(13)(14)(15)(16). In addition, a large number of studies have shown that cell-free ncRNAs have been dysregulated in the serum, plasma, urine, and peripheral blood samples of patients with T2D (17)(18)(19)(20). The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), also termed nuclear enriched abundant transcript 2 (NEAT2), is one of the ncRNAs in human disease that has received the most attention from researchers, especially in diabetes and diabetic-related complications (21,22).…”