LncRNA LEGLTBC Functions as a ceRNA to Antagonize the Effects of miR-34a on the Downregulation of SIRT1 in Glucolipotoxicity-Induced INS-1 Beta Cell Oxidative Stress and Apoptosis

Xiang, Kuanhui; Liu, Chongxiao; Wang, Guodong; Yang, Hui; Yao, Xin-ming; Hua, Qiang; Li, Xiaoyong; Zhang, Hongmei; Moody, M. Anthony; Su, Qing; Lv, Kun

doi:10.1155/2019/4010764

Cited by 34 publications

(32 citation statements)

References 35 publications

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“…Detailed in vitro studies revealed that HOTAIR served as a sponge for miR-34a, where upregulation of the latter was connected with downregulation of SIRT1, decreased signaling via FOXO1, along with the burst of OxS, inflammation and induction of apoptosis [178]. A similar mechanism of action was reported for another long-non-coding RNA (lncRNA), low expression in glucolipotoxicity-treated beta cells (LEGLTBC), in the course of glucolipotoxicity of pancreatic β-cells [179]. Further, in retinal epithelial cells exposed to HG, another downregulated lncRNA, maternally expressed gene 3 (MEG3), was demonstrated reported to affect miR-34/SIRT1 axis [180].…”

Section: Mirnas In Mets-a Link With Obesity and Insulin Resistance/hymentioning

confidence: 66%

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

Włodarski

Strycharz

Wróblewski

et al. 2020

IJMS

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Oxidative stress (OxS) is the cause and the consequence of metabolic syndrome (MetS), the incidence and economic burden of which is increasing each year. OxS triggers the dysregulation of signaling pathways associated with metabolism and epigenetics, including microRNAs, which are biomarkers of metabolic disorders. In this review, we aimed to summarize the current knowledge regarding the interplay between microRNAs and OxS in MetS and its components. We searched PubMed and Google Scholar to summarize the most relevant studies. Collected data suggested that different sources of OxS (e.g., hyperglycemia, insulin resistance (IR), hyperlipidemia, obesity, proinflammatory cytokines) change the expression of numerous microRNAs in organs involved in the regulation of glucose and lipid metabolism and endothelium. Dysregulated microRNAs either directly or indirectly affect the expression and/or activity of molecules of antioxidative signaling pathways (SIRT1, FOXOs, Keap1/Nrf2) along with effector enzymes (e.g., GPx-1, SOD1/2, HO-1), ROS producers (e.g., NOX4/5), as well as genes of numerous signaling pathways connected with inflammation, insulin sensitivity, and lipid metabolism, thus promoting the progression of metabolic imbalance. MicroRNAs appear to be important epigenetic modifiers in managing the delicate redox balance, mediating either pro- or antioxidant biological impacts. Summarizing, microRNAs may be promising therapeutic targets in ameliorating the repercussions of OxS in MetS.

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Section: Mirnas In Mets-a Link With Obesity and Insulin Resistance/hymentioning

confidence: 66%

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

Włodarski

Strycharz

Wróblewski

et al. 2020

IJMS

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“…Recently, ceRNAs, which indicate lncRNAs that can manipulate other transcripts by competing for binding to microRNAs, have attracted increasing attention [35,36]. The lncRNA LEGLTBC has been discovered to act as a ceRNA to antagonize the impacts of miR-34a on the downregulation of SIRT1 in glucolipotoxicity-induced INS-1 beta cell oxidative stress and apoptosis [37]. As a ceRNA, LINC00511 was also found to facilitate cell malignant behaviours and relate to hepatocellular carcinoma patient prognosis by interfering with the miR-195/EYA1 axis [38].…”

Section: Discussionmentioning

confidence: 99%

LncRNA CASC2 Alleviates the Progression of Diabetic Nephropathy by Regulating the miR-144/SOCS2 Signalling Axis

Min

Xie

2020

Kidney Blood Press Res

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Background: Diabetic nephropathy constitutes a large proportion of end-stage kidney failure in diabetic patients. However, the underlying molecular mechanisms remain unclear. Methods: Db/db diabetic mouse models and high glucose (HG)-induced human renal mesangial cells (HRMCs) were used as research models in vivo and in vitro. The expression of cancer susceptibility candidate 2 (CASC2) was quantified by qRT-PCR. The regulatory role of CASC2 in cell apoptosis, inflammatory factor release, and fibrosis was verified by flow cytometry, qRT-PCR, and Western blot assay, respectively. The bioinformatics prediction software DIANA and starBase v2.0 were used to predict the putative binding sites. The interactions among CASC2, miR-144, and SOCS2 were explored by the luciferase assay and Western bolt assay. Results: The expression of CASC2 in diabetic mouse models and HG-induced HRMCs was lower than that in the control (p < 0.05). Overexpression of CASC2 resulted in a decrease in the apoptosis rate, inflammatory factor release (TNF-α, IL-6, and IL-1β), expression of cleaved caspase-3, and fibrotic proteins (fibronectin, Col-IV, and TGF-β1) and an increase in Bcl-2 expression. Inhibition of CASC2 caused increased expression of miR-144. Furthermore, mechanistic investigations confirmed that activation of the miR-144/SOCS2 regulatory loop by overexpression of miR‐144 reversed the in vitro effects of CASC2 on inhibiting cell apoptosis, inflammatory factor release, and fibrosis. In addition, simultaneous overexpression of miR-144 and SOCS2 further increased the inhibition of cell apoptosis, inflammatory factor release, and fibrosis by CASC2. Conclusion: CASC2 could alleviate the degree and process of apoptosis, inflammation, and fibrosis in diabetic nephropathic models by regulating the miR-144/SOCS2 axis.

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“…LncRNAs can act as miRNA sponges to regulate mRNA expression and activity via the ceRNA mechanism[ 24 ]. Recently, studies have revealed that lncRNAs are involved in the process of insulin secretion and β cell apoptosis through the ceRNA mechanism[ 41 , 42 ]. In this study, we identified seven lncRNAs (NONRATT002662, NONRATT005090, NONRATT005619, NONRATT019513, NONRATT027738, NONRATT027888, and NONRATT030038) that competitively bind to six miRNAs (rno-miR-449a-5p, rno-miR-5132-3p, rno-miR-344g, rno-miR-3075, rno-miR-378a-5p, and rno-miR-874-3p), thereby influencing the expression and function of hub mRNAs ( Pomc , Htr2a , and Agtr1a ).…”

Section: Discussionmentioning

confidence: 99%

Analysis of long noncoding RNA-associated competing endogenous RNA network in glucagon-like peptide-1 receptor agonist-mediated protection in β cells

Bai¹,

Zhi²,

Liu³

et al. 2020

WJD

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BACKGROUND Long noncoding RNAs (lncRNAs) and mRNAs are widely involved in various physiological and pathological processes. The use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) is a novel therapeutic strategy that could promote insulin secretion and decrease the rate of β-cell apoptosis in type 2 diabetes mellitus (T2DM) patients. However, the specific lncRNAs and mRNAs and their functions in these processes have not been fully identified and elucidated. AIM To identify the lncRNAs and mRNAs that are involved in the protective effect of GLP-1RA in β cells, and their roles. METHODS Rat gene microarray was used to screen differentially expressed (DE) lncRNAs and mRNAs in β cells treated with geniposide, a GLP-1RA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to assess the underlying functions of DE mRNAs. Hub mRNAs were filtered using the STRING database and the Cytoscape plugin, CytoHubba. In order to reveal the regulatory relationship between lncRNAs and hub mRNAs, their co-expression network was constructed based on the Pearson coefficient of DE lncRNAs and mRNAs, and competing endogenous RNA (ceRNA) mechanism was explored through miRanda and TargetScan databases. RESULTS We identified 308 DE lncRNAs and 128 DE mRNAs with a fold change filter of ≥ 1.5 and P value < 0.05. GO and KEGG pathway enrichment analyses indicated that the most enriched terms were G-protein coupled receptor signaling pathway, inflammatory response, calcium signaling pathway, positive regulation of cell proliferation, and ERK1 and ERK2 cascade. Pomc , Htr2a , and Agtr1a were screened as hub mRNAs using the STRING database and the Cytoscape plugin, CytoHubba. This result was further verified using SwissTargetPrediction tool. Through the co-expression network and competing endogenous (ceRNA) mechanism, we identified seven lncRNAs (NONRATT027738, NONRATT027888, NONRATT030038, etc .) co-expressed with the three hub mRNAs ( Pomc, Htr2a, and Agtr1a ) based on the Pearson coefficient of the expression levels. These lncRNAs regulated hub mRNA functions by competing with six miRNAs ( r no-miR-5132-3p, rno-miR-344g, rno-miR-3075, etc .) via the ceRNA mechanism. Further analysis indicated that lncRNA NONRATT027738 interacts with all the three hub mRNAs, suggesting that it is at a core position within the ceRNA network. CONCLUSION We have identified key lncRNAs and mRNAs, and highlighted here how they interact through the ceRNA mechanism to mediate the protective effect of GLP-1RA in β cells.

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LncRNA LEGLTBC Functions as a ceRNA to Antagonize the Effects of miR-34a on the Downregulation of SIRT1 in Glucolipotoxicity-Induced INS-1 Beta Cell Oxidative Stress and Apoptosis

Cited by 34 publications

References 35 publications

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

LncRNA CASC2 Alleviates the Progression of Diabetic Nephropathy by Regulating the miR-144/SOCS2 Signalling Axis

Analysis of long noncoding RNA-associated competing endogenous RNA network in glucagon-like peptide-1 receptor agonist-mediated protection in β cells

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