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Long non-coding RNA MIAT is involved in the regulation of pyroptosis in diabetic cardiomyopathy via targeting miR-214-3p.

ABSTRACT: Diabetic cardiomyopathy (DCM) is one of the most common complications of diabetes without effective treatment options. Its pathogenesis is complex and remains unclear. Long non-coding RNA (lncRNA) MIAT allele has been reported to be enriched in DCM patients and activate a pyroptosis program in hypoxia-induced H9c2 cells. Thus, whether MIAT played a role in DCM pyroptosis remains to be clarified. In the study, the expression of MIAT was found elevated in the serum of diabetic patients, as well as in high-glucose induced cardiomyocytes and diabetic mice. Further, the expression levels of CASP1 and pyroptosis correlation factors (IL-1 and IL-18) were downregulated after silencing MIAT. Through modeling and validation experiments, we then confirmed that the MIAT-miR-214-3p-CASP1 axis serves as an essential point in pyroptosis of DCM mice. These results suggested that silencing MIAT would be a potential treatment strategy for DCM.

SUBMITTER: Xiao W

PROVIDER: S-EPMC8671938 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Long non-coding RNA MIAT is involved in the regulation of pyroptosis in diabetic cardiomyopathy via targeting miR-214-3p.

Xiao Wenjing W Zheng Dezhi D Chen Xin X Yu Botao B Deng Kaiwen K Ma Jie J Wen Xudong X Hu Yonghe Y Hou Jun J

iScience 20211126 12

Diabetic cardiomyopathy (DCM) is one of the most common complications of diabetes without effective treatment options. Its pathogenesis is complex and remains unclear. Long non-coding RNA (lncRNA) MIAT allele has been reported to be enriched in DCM patients and activate a pyroptosis program in hypoxia-induced H9c2 cells. Thus, whether MIAT played a role in DCM pyroptosis remains to be clarified. In the study, the expression of MIAT was found elevated in the serum of diabetic patients, as well as ...[more]

PMID: 34950859

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Project description:BackgroundAngiogenesis and metastasis contributes substantially to the poor outcome of patients with ovarian cancer. We aimed to explore the role and mechanisms of the long non-coding RNA NEAT1 (nuclear enriched abundant transcript 1) in regulating angiogenesis and metastasis of human ovarian cancer. NEAT1 expression in human ovarian cancer tissues and cell lines including SKOV-3 and A2780 was investigated through in situ hybridization. Gene knockdown and overexpressing were achieved through lentivirus infection, transfection of plasmids or microRNA mimics. Cell viability was measured with the cell counting kit-8 assay, while apoptosis was determined by flow cytometry. Cell migration and invasion were evaluated by transwell experiments, and protein expression was determined by western blot assays or immunohistochemistry. Duo-luciferase reporter assay was employed to confirm the interaction between NEAT1 and target microRNA. In vivo tumor growth was evaluated in nude mice with xenografted SKOV-3/A2780 cells, and blood vessel formation in tumor was examined by histological staining.ResultsNEAT1 was highly expressed in ovarian cancer tissues of patients and cell lines. MiR-214-3p was identified as a sponging target of NEAT1, and they antagonizedeach other in a reciprocal manner. NEAT1-overexpressing SKOV-3 and A2780 cells had significantly increased proliferation, reduced apoptosis, and augmented abilities of migration and invasion, while cells with NEAT1-knockdown displayed markedly attenuated traits of malignancies. Additionally, the levels of NEAT1 appeared to be positively correlated with the expression levels of angiogenesis-related molecules, including Semaphorin 4D (Sema4D), Sema4D receptor Plexin B1, T-lymphoma invasion and metastasis-inducing protein-1 (Tiam1), and Rho-like GTPases Rac1/2/3. In the xenograft mouse model, more NEAT1 expression resulted in faster in vivo tumor growth, more blood vessel formation in tumor tissues, as well as higher expression levels of angiogenesis-related molecules and CD31.ConclusionsNEAT1 promotes angiogenesis and metastasis in human ovarian cancer. NEAT1 and miR-214-3p are promising targets for developing therapeutics to treat human ovarian cancer.

Project description:BackgroundNoncoding RNAs play pivotal roles in the process of autoimmune diseases. However, the definite contributions of these molecules to Behçet's disease (BD) are still unknown. This study aimed to explore the clinical value of a novel competing endogenous (ce) RNA network in the pathogenesis of BD and to assess its use in primary diagnosis.MethodsBioinformatic analysis was applied to construct a BD-related ceRNA network: lncRNA (MIAT and PVT1)-miRNA (miR-93-5p and miR-124-3p)-mRNA (SOD-2 and MICA). Blood was obtained from 70 BD patients and 30 healthy subjects, and the serum expression of the tested RNAs was estimated via quantitative real-time PCR (qPCR). Serum tumor necrosis factor-alpha (TNF-α) levels were also determined. The associations between these RNAs were further analyzed, and receiver operating characteristic (ROC) curve and logistic regression analyses were employed to validate their diagnostic and prognostic values.ResultsThe expression levels of the lncRNAs PVT1 and miR-93-5p were significantly increased, whereas those of the lncRNAs MIAT and miR-124-3p, as well as those of the SOD-2 and MICA mRNAs, were significantly decreased in BD patients compared with controls. BD patients had significantly higher serum TNF-α levels than controls did. ROC curve analysis indicated that the selected RNAs could be candidate diagnostic biomarkers for BD. Moreover, the highest diagnostic efficiency was achieved with the combination of MIAT and miR-93-5p or PVT1 and miR-124-3p with either SOD-2 or MICA. Logistic regression analysis revealed that all RNA expression levels could be predictors for BD.ConclusionMechanistically, our research revealed a novel ceRNA network that is significantly disrupted in BD. The findings reported herein, highlight the noncoding RNA-molecular pathways underlying BD and identify potential targets for therapeutic intervention. These insights will likely be applicable for developing new strategies for the early diagnosis, management and risk assessment of BD as well as the design of novel preventive measures. Trial registration The protocol for the clinical studies was approved by Cairo University's Faculty of Pharmacy's Research Ethics Committee (approval number: BC 3590).

Dataset Information

Long non-coding RNA MIAT is involved in the regulation of pyroptosis in diabetic cardiomyopathy via targeting miR-214-3p.

Publications

Long non-coding RNA MIAT is involved in the regulation of pyroptosis in diabetic cardiomyopathy via targeting miR-214-3p.

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