NEAT1: A Novel Long Non-coding RNA Involved in Mediating Type 2 Diabetes and
its Various Complications

Jia, Dengke; He, Yong; Wang, Yaqi; Xue, Mengzhen; Zhu, Leiqi; Xia, Fangqi; Li, Yuanyang; Gao, Yan; Li, Luoying; Chen, Silong; Xu, Guangyan; Yuan, Chengfu

doi:10.2174/1381612828666220428093207

Cited by 11 publications

(4 citation statements)

References 66 publications

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“…For example, MALAT1 was upregulated in brain tissues of individuals with T2DM-OSA, and its knockdown inhibited the hippocampal inflammatory response in T2DM-OSA [ 14 ]. NEAT1, a member of the lncRNA family, is closely correlated with T2DM progression and impacts T2DM prognosis [ 26 ]. A study revealed that NEAT1 promoted diabetic retinopathy progression [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

LncRNA NEAT1 aggravates human microvascular endothelial cell injury by inhibiting the Apelin/Nrf2/HO-1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoea

Chen,

Ou,

Huang

et al. 2024

Epigenetics

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Long noncoding RNAs (lncRNAs) regulate the progression of type 2 diabetes mellitus complicated with obstructive sleep apnoea (T2DM-OSA). However, the role of the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in T2DM-OSA remains unknown. This study aimed to reveal the function of NEAT1 in T2DM-OSA and the underlying mechanism. KKAy mice were exposed to intermittent hypoxia (IH) or intermittent normoxia to generate a T2DM-OSA mouse model. HMEC-1 cells were treated with high glucose (HG) and IH to construct a T2DM-OSA cell model. RNA expression was detected by qRT-PCR. The protein expression of Apelin, NF-E2-related factor 2 (Nrf2), haem oxygenase-1 (HO-1), and up-frameshift suppressor 1 (UPF1) was assessed using western blot. Cell injury was evaluated using flow cytometry, enzyme-linked immunosorbent assay, and oxidative stress kit assays. RIP, RNA pull-down, and actinomycin D assays were performed to determine the associations between NEAT1, UPF1, and Apelin. NEAT1 expression was upregulated in the aortic vascular tissues of mice with T2DM exposed to IH and HMEC-1 cells stimulated with HG and IH, whereas Apelin expression was downregulated. The absence of NEAT1 protected HMEC-1 cells from HG- and IH-induced damage. Furthermore, NEAT1 destabilized Apelin mRNA by recruiting UPF1. Apelin overexpression decreased HG- and IH-induced injury to HMEC-1 cells by activating the Nrf2/HO-1 pathway. Moreover, NEAT1 knockdown reduced HG- and IH-induced injury to HMEC-1 cells through Apelin. NEAT1 silencing reduced HMEC-1 cell injury through the Apelin/Nrf2/HO-1 signalling pathway in T2DM-OSA. Abbreviations: LncRNAs, long non-coding RNAs; T2DM, type 2 diabetes mellitus; OSA, obstructive sleep apnoea; NEAT1, nuclear paraspeckle assembly transcript 1; IH, intermittent hypoxia; HMEC-1, human microvascular endothelial cells; HG, high glucose; Nrf2, NF-E2-related factor 2; UPF1, up-frameshift suppressor 1; HO-1, haem oxygenase-1; qRT-PCR, quantitative real-time polymerase chain reaction; ELISA, enzyme-linked immunosorbent assay; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; TNF-α, tumour necrosis factor-α; CCK-8, Cell Counting Kit-8; IL-1β, interleukin-1β; ROS, reactive oxygen species; MDA, malondialdehyde; SOD, superoxide dismutase; RIP, RNA immunoprecipitation; SD, standard deviations; GSH, glutathione; AIS, acute ischaemic stroke; HMGB1, high mobility group box-1 protein; TLR4, toll-like receptor 4.

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Section: Discussionmentioning

confidence: 99%

LncRNA NEAT1 aggravates human microvascular endothelial cell injury by inhibiting the Apelin/Nrf2/HO-1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoea

Chen,

Ou,

Huang

et al. 2024

Epigenetics

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“…MEG3 is downregulated in the islets and blood of individuals with diabetes, and in a murine β-cell line (MIN6), MEG3 seems to regulate insulin synthesis and secretion since its absence reduced the expression of key factors for β-cell function ( PDX-1 and MAFA ), decreasing insulin synthesis [ 8 , 52 ]. NEAT1 is overexpressed in individuals, and it is highly expressed in hyperglycemia conditions affecting inflammatory pathways [ 53 , 54 ]. MIR7-3HG was shown to ameliorate dexamethasone-induced dysfunction in β-cells through the PI3K-AKT signaling pathway [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Gene expression analysis reveals diabetes-related gene signatures

Farrim,

Gomes,

Milenkovic

et al. 2024

Hum Genomics

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Background Diabetes is a spectrum of metabolic diseases affecting millions of people worldwide. The loss of pancreatic β-cell mass by either autoimmune destruction or apoptosis, in type 1-diabetes (T1D) and type 2-diabetes (T2D), respectively, represents a pathophysiological process leading to insulin deficiency. Therefore, therapeutic strategies focusing on restoring β-cell mass and β-cell insulin secretory capacity may impact disease management. This study took advantage of powerful integrative bioinformatic tools to scrutinize publicly available diabetes-associated gene expression data to unveil novel potential molecular targets associated with β-cell dysfunction. Methods A comprehensive literature search for human studies on gene expression alterations in the pancreas associated with T1D and T2D was performed. A total of 6 studies were selected for data extraction and for bioinformatic analysis. Pathway enrichment analyses of differentially expressed genes (DEGs) were conducted, together with protein–protein interaction networks and the identification of potential transcription factors (TFs). For noncoding differentially expressed RNAs, microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), which exert regulatory activities associated with diabetes, identifying target genes and pathways regulated by these RNAs is fundamental for establishing a robust regulatory network. Results Comparisons of DEGs among the 6 studies showed 59 genes in common among 4 or more studies. Besides alterations in mRNA, it was possible to identify differentially expressed miRNA and lncRNA. Among the top transcription factors (TFs), HIPK2, KLF5, STAT1 and STAT3 emerged as potential regulators of the altered gene expression. Integrated analysis of protein-coding genes, miRNAs, and lncRNAs pointed out several pathways involved in metabolism, cell signaling, the immune system, cell adhesion, and interactions. Interestingly, the GABAergic synapse pathway emerged as the only common pathway to all datasets. Conclusions This study demonstrated the power of bioinformatics tools in scrutinizing publicly available gene expression data, thereby revealing potential therapeutic targets like the GABAergic synapse pathway, which holds promise in modulating α-cells transdifferentiation into β-cells.

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“…LncRNA NEAT1 (nuclear-enriched abundant transcript 1) is involved not only in atherosclerosis 42,44 or aneurysm 50 but has shortly been mentioned as being also dysregulated in DM, especially in diabetic neuropathy and diabetic kidney disease [51][52][53][54] . Furthermore, NEAT1 has already been described as having a critical in the phenotypic switching of SMCs by repressing SM-contractile gene expression through an epigenetic regulatory mechanism 16 .…”

Section: Discussionmentioning

confidence: 99%

Transcriptomics analysis of long non-coding RNAs in smooth muscle cells from patients with peripheral artery disease and diabetes mellitus

Yundung,

Mohammed,

Paneni

et al. 2024

Preprint

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Diabetes mellitus (DM) is a significant risk factor for peripheral arterial disease (PAD), and PAD is an independent predictor of cardiovascular disorders (CVDs). Growing evidence suggests that long non-coding RNAs (lncRNAs) significantly contribute to disease development and underlying complications, particularly affecting smooth muscle cells (SMCs). So far, no study has focused on transcriptome analysis of lncRNAs in PAD patients with and without DM. Tissue samples were obtained from our Vascular Biobank. Due to the sample’s heterogeneity, expression analysis of lncRNAs in whole tissue detected only ACTA2-AS1 with 4.9-fold increase in PAD patients with DM. In contrast, transcriptomics of SMCs revealed 28 lncRNAs significantly differentially expressed between PAD with and without DM (FDR < 0.1). Sixteen lncRNAs were of unknown function, six were described in cancer, one connected with macrophages polarisation, and five were associated with CVDs, mainly with SMC function and phenotypic switch (NEAT1, XIST, MIR222HG, MIR100HG, HIF1A-AS3, MRI29B2CHG). The enrichment analysis revealed additional lncRNAs H19, CARMN, FTX, and MEG3 linked with DM. Our study revealed several lncRNAs in diabetic PAD patients associated with the physiological function of SMCs. These lncRNAs might serve as potential therapeutic targets to improve the function of SMCs within the diseased tissue and, thus, the clinical outcome.

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NEAT1: A Novel Long Non-coding RNA Involved in Mediating Type 2 Diabetes and its Various Complications

Cited by 11 publications

References 66 publications

LncRNA NEAT1 aggravates human microvascular endothelial cell injury by inhibiting the Apelin/Nrf2/HO-1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoea

LncRNA NEAT1 aggravates human microvascular endothelial cell injury by inhibiting the Apelin/Nrf2/HO-1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoea

Gene expression analysis reveals diabetes-related gene signatures

Transcriptomics analysis of long non-coding RNAs in smooth muscle cells from patients with peripheral artery disease and diabetes mellitus

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