LncRNA H19 inhibits autophagy by epigenetically silencing of DIRAS3 in diabetic cardiomyopathy

Zhuo, Chuanjun; Jiang, Ronghuan; Lin, Xiaodong; Shao, Mingjing

doi:10.18632/oncotarget.13637

Cited by 121 publications

(112 citation statements)

References 25 publications

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“…Specific roles of H19 in tumourigenesis are disputable as it harbours pro-tumourigenic [22] and tumour-suppressive [21,23] properties. In diabetes, exposure to high glucose levels reduced H19 expression in neonatal cardiomyocytes, and in the myocardium of streptozotocin (STZ)-induced diabetes in rats used as a model of diabetes [24]. H19 has also been shown to alter the microRNA (miR)-200 pathway by increasing upstream histone acetylation, thus reversing EMT [23].…”

Section: Introductionmentioning

confidence: 99%

lncRNA H19 prevents endothelial–mesenchymal transition in diabetic retinopathy

et al. 2019

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Aims/hypothesis The pathophysiology of diabetic retinopathy is linked to hyperglycaemia and its effect on retinal microvascular tissues. The resulting endothelial injury changes the endothelial cell phenotype to acquire mesenchymal properties (i.e. endothelial-mesenchymal transition [EndMT]). Such changes can be regulated by epigenetic mechanisms, including long non-coding RNAs (lncRNAs). lncRNA H19 may influence EndMT through TGF-β. We investigated the role of H19 in regulating EndMT during diabetic retinopathy. Methods H19 was overexpressed or silenced in human retinal endothelial cells exposed to various glucose levels. The cells were examined for H19, endothelial and mesenchymal markers. We then expanded the study to retinal tissues in a mouse model of diabetic retinopathy and also examined vitreous humour samples from individuals with proliferative diabetic retinopathy. Results Expression of H19 was downregulated in high glucose conditions (25 mmol/l). H19 overexpression prevented glucoseinduced EndMT. Such changes appear to involve TGF-β through a Smad-independent mechanism. Diabetes caused downregulation of retinal H19. Using H19 knockout mice, we demonstrated similar EndMT in the retina. Examination of vitreous humour from individuals with proliferative diabetic retinopathy also reinforced the downregulation of H19 in diabetes. Conclusions/interpretationWe therefore concluded that H19 regulates EndMT in diabetic retinopathy through specific mechanisms. Data availability The results from our previous microarray can be found online using the GEO accession number GSE122189.

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Section: Introductionmentioning

confidence: 99%

lncRNA H19 prevents endothelial–mesenchymal transition in diabetic retinopathy

et al. 2019

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“…Zhang et al also found that the expression of lncRNA MALAT1 was increased dramatically in DCM rat cardiomyocytes and was closely related to its cardiac contractile function . The study of Zhuo et al showed that lncRNA H19 could silence DIRAS3 epigenetically and inhibit autophagy in diabetic cardiomyocytes . Zhang's team study showed that by inhibiting lncRNA‐AK081284, interleukin‐17 ablation reduced cardiac interstitial fibrosis and improved cardiac function in diabetic mice .…”

Section: Long Noncoding Rnasmentioning

confidence: 98%

“…68 The study of Zhuo et al showed that lncRNA H19 could silence DIRAS3 epigenetically and inhibit autophagy in diabetic cardiomyocytes. 69 Zhang's team study showed that by inhibiting lncRNA-AK081284, interleukin-17 ablation reduced cardiac interstitial fibrosis and improved cardiac function in diabetic mice. 4 Gonzalo-Calvo et al indicated that lncRNAs are independent predictors of diastolic function and remodelling in patients with type 2 diabetes.…”

Section: Long Noncoding Rnasmentioning

confidence: 99%

Long noncoding RNAs: A new player in the prevention and treatment of diabetic cardiomyopathy?

Luo

Liu

et al. 2018

Diabetes Metabolism Res

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Diabetic cardiomyopathy (DCM) can cause extensive necrosis of the heart muscle by metabolic disorders and microangiopathy, with subclinical cardiac dysfunction, and eventually progress to heart failure, arrhythmia, and cardiogenic shock; severe patients may even die suddenly. Long noncoding RNAs (lncRNAs) are a class of nonprotein-coding RNAs longer than 200 nucleotides. They have critical roles in various biological processes, including gene expression regulation, genomic imprinting, nuclear-cytoplasmic trafficking, RNA splicing, and translational control. Recent studies indicated that lncRNAs extensively participate in the development of diverse cardiac diseases, such as cardiac ischaemia, hypertrophy, and heart failure. Little is known about lncRNA in DCM. In this review, we summarize the current literature on lncRNAs in DCM studies, aiming to provide new methods for DCM's future prevention and treatment strategies.

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“…LncRNAs have been reported to be associated with the development of various cancers (7,14,19,20). To identify lncRNAs that are involved in the development of ATL, we first examined the expression of selected onco-lncRNAs in HTLV-1-infected cell lines.…”

Section: Lncrna Anril Is Up-regulated In Atlmentioning

confidence: 99%

“…PRC2 has been demonstrated to be a functional target of some lncRNA, e.g., ANRIL, HOTAIR, Fendrr, H19, MALAT1, and COLDAIR (14,15,(17)(18)(19)(20)(21). Moreover, PRC2/lncRNA complex-mediated dynamic control of H3K27 trimethylation (H3K27me3) is central to gene silencing in various cellular processes (8,22).…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA ANRIL supports proliferation of adult T-cell leukemia cells through cooperation with EZH2

Song

Chen

et al. 2018

Preprint

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word count: 196 2 Text word count: 4470 3 ABSTRACT Adult T-cell leukemia (ATL) is a highly aggressive T-cell malignancy induced by human T-cell leukemia virus type 1 (HTLV-1) infection. Long noncoding RNA (lncRNA) plays a critical role in the development and progression of multiple human cancers. However, the function of lncRNA on HTLV-1-induced oncogenesis has not been elucidated. In the present study, we show that the expression of the lncRNA ANRIL was elevated in HTLV-1 infected cell lines and clinical ATL samples. E2F1 induced ANRIL transcription by enhancing its promoter activity. Knocking down of ANRIL in ATL cells repressed cellular proliferation and increased apoptosis in vitro and in vivo.As a mechanism for these actions, we found that ANRIL targeted EZH2, and activated the NF-κB pathway in ATL cells. This activation was independent of the histone methyltransferase (HMT) activity of EZH2, but required the formation of an ANRIL/EZH2/p65 ternary complex. Chromatin immunoprecipitation assay revealed that ANRIL/EZH2 enhanced p65 DNA binding capability. In addition, we observed that ANRIL/EZH2 complex repressed p21/CDKN1A transcription through H3K27 trimethylation of the p21/CDKN1A promoter. Taken together, our results implicate that lncRNA ANRIL, by cooperating with EZH2, supports the proliferation of HTLV-1 infected cells, which is thought to be critical for oncogenesis. IMPORTANCEHuman T-cell leukemia virus type 1 (HTLV-1) is the pathogen that causes adult T-cell leukemia (ATL), which is a unique malignancy of CD4+ T cells. A role for long noncoding RNA (lncRNA) in HTLV-1-mediated cellular transformation has not been described. In this study, we demonstrated that lncRNA ANRIL was important for maintaining proliferation of ATL cells in vitro and in vivo. ANRIL was shown to activate NF-κB signaling through forming a ternary complex with EZH2 and p65.Further, epigenetic inactivation of p21/CDKN1A was involved in the oncogenic function of ANRIL. To the best of our knowledge, this is the first study to address the regulatory role of the lncRNA ANRIL in ATL and provides an important clue to prevent or treat HTLV-1 associated human diseases. KEYWORDSATL, HTLV-1, ANRIL, EZH2, NF-κBWe thank Caryl Antalis for proof-reading of this manuscript.

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LncRNA H19 inhibits autophagy by epigenetically silencing of DIRAS3 in diabetic cardiomyopathy

Cited by 121 publications

References 25 publications

lncRNA H19 prevents endothelial–mesenchymal transition in diabetic retinopathy

lncRNA H19 prevents endothelial–mesenchymal transition in diabetic retinopathy

Long noncoding RNAs: A new player in the prevention and treatment of diabetic cardiomyopathy?

Long noncoding RNA ANRIL supports proliferation of adult T-cell leukemia cells through cooperation with EZH2

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