Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway

Jin, Xin; Hao, Jin; Shi, Yan; Guo, Yiyuan; Zhang, Hong

doi:10.1159/000477330

Cited by 63 publications

(53 citation statements)

References 34 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Guo et al [27] suggested that Kcnq1ot1 could regulate MET expression to promote melanoma growth via binding to miR-153. In our study, the bioinformatics assay predicted that miR-214-3p was a ceRNA of Kcnq1ot1 and had binding sites for both Kcnq1ot1 and caspase-1, which was consistent with the results of previous study on cataracts [18]. We elaborated for the first time the downregulation of miR-214-3p in high glucose-treated cardiomyocytes and the effect of Kcnq1ot1 on DCM via miR-214-3p and caspase-1.…”

Section: Discussionsupporting

confidence: 90%

“…2G). The ceRNA networks between Kcnq1ot1 and miR-214-3p and between caspase-1 and miR-214-3p were demonstrated in a previous study using the luciferase assay [18].…”

Section: Silencing Kcnq1ot1 By Sirna Inhibits Pyroptosis Of Cardiomyomentioning

confidence: 67%

“…A recent study found that Kcnq1ot1 might act as a ceRNA to regulate the expression of caspase-1 via sponging miR-214-3p to influence cataract formation [18]. However, whether Kcnq1ot1 can regulate pyroptosis in DCM is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

LncRNA KCNQ1OT1 Mediates Pyroptosis in Diabetic Cardiomyopathy

Yang

Qin

Wang

et al. 2018

Cell Physiol Biochem

142

109

View full text Add to dashboard Cite

Background/Aims: Diabetic cardiomyopathy (DCM) is a common complication of diabetes and can cause heart failure, arrhythmia and sudden death. The pathogenesis of DCM includes altered metabolism, mitochondrial dysfunction, oxidative stress, inflammation, cell death and extracellular matrix remodeling. Recently, pyroptosis, a type of programmed cell death related to inflammation, was proven to be activated in DCM. However, the molecular mechanisms underlying pyroptosis in DCM remain elusive. The long non-coding RNA (lncRNA) Kcnq1ot1 participates in many cardiovascular diseases. This study aims to clarify whether Kcnq1ot1 affects cardiac pyroptosis in DCM. Methods: AC16 cells and primary cardiomyocytes were incubated with 5.5 and 50 mmol/L glucose. Diabetic mice were induced with streptozotocin (STZ). Kcnq1ot1 was silenced both in vitro and in vivo. qRT-PCR was used to detect the expression level of Kcnq1ot1. Immunofluorescence, qRT-PCR and western blot analyses were used to detect the degree of pyroptosis. Echocardiography, hematoxylin and eosin staining, and Masson’s trichrome staining were used to detect the cardiac function and morphology in mice. Cell death and function were detected using TUNEL staining, immunofluorescence staining and Ca²⁺ measurements. Results: The expression of Kcnq1ot1 was increased in patients with diabetes, high glucose-induced cardiomyocytes and diabetic mouse cardiac tissue. Silencing Kcnq1ot1 alleviated pyroptosis by targeting miR-214-3p and caspase-1. Furthermore, silencing Kcnq1ot1 reduced cell death, cytoskeletal structure abnormalities and calcium overload in vitro and improved cardiac function and morphology in vivo. Conclusion: Kcnq1ot1 is overexpressed in DCM, and silencing Kcnq1ot1 inhibits pyroptosis by influencing miR-214-3p and caspase-1 expression. We clarified for the first time that Kcnq1ot1 could be a new therapeutic target for DCM.

show abstract

Section: Discussionsupporting

confidence: 90%

“…2G). The ceRNA networks between Kcnq1ot1 and miR-214-3p and between caspase-1 and miR-214-3p were demonstrated in a previous study using the luciferase assay [18].…”

Section: Silencing Kcnq1ot1 By Sirna Inhibits Pyroptosis Of Cardiomyomentioning

confidence: 67%

See 1 more Smart Citation

LncRNA KCNQ1OT1 Mediates Pyroptosis in Diabetic Cardiomyopathy

Yang

Qin

Wang

et al. 2018

Cell Physiol Biochem

142

109

View full text Add to dashboard Cite

show abstract

“…Critical enzymes involved in DNA methylation, such as DNMT1 and MeCP2, have been identified in human lens epithelial cells (HLECs) [10,11]. Epigenetic regulatory processes, including DNA methylation of CRYAA [9,10,[12][13][14], histone acetylation of SOD1 [15] and long non-coding RNA (lncRNA)-MIAT and KCNQ1OT1 [16,17], have been implicated in the pathological cataractogenesis.…”

Section: Introductionmentioning

confidence: 99%

Long Non-Coding RNA H19 Regulates Human Lens Epithelial Cells Function

Liu

Shan

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Age-related cataract (ARC) remains the leading cause of visual impairment among the elderly population. Long non-coding RNAs (lncRNAs) have emerged as potential regulators in many ocular diseases. However, the role of lncRNAs in nuclear ARC, a subtype of ARC, requires further elucidation. Methods: LncRNA sequencing was performed to identify differentially expressed lncRNAs between the capsules of transparent and nuclear ARC lenses. Expression validation was confirmed by qRT-PCR. MTT assay, Calcein-AM and propidium iodide double staining, Rhodamine 123 and Hoechst double staining, EdU and transwell assay were used to determine the role of H19 or miR-675 in the viability, apoptosis, proliferation and migration of primary cultured human lens epithelial cells (HLECs). Bioinformatics and luciferase reporter assays were used to identify the binding target of miR-675. Results: Sixty-three lncRNAs are differentially expressed between the capsules of transparent and nuclear ARC lenses. One top abundantly expressed lncRNA, H19, is significantly up-regulated in the nuclear ARC lens capsules and positively associated with nuclear ARC grade. H19 knockdown accelerates apoptosis development and reduces the proliferation and migration of HLECs upon oxidative stress. H19 is the precursor of miR-675, and a reduction of H19 inhibits miR-675 expression. miR-675 regulates CRYAA expression by targeting the binding site within the 3’UTR. Moreover, miR-675 increases the proliferation and migration while decreasing the apoptosis of HLECs upon oxidative stress. Conclusion: H19 regulates HLECs function through miR-675-mediated CRYAA expression. This finding would provide a novel insight into the pathogenesis of nuclear ARC.

show abstract

“…To date, accumulating evidence has been confirmed a close relation between miRNA and the pathogenesis of various ocular diseases, such as pterygium, retinoblastoma, and glaucoma [9,10], as well as cataract. For example, Jin et al [11] revealed that long-chain non-coding RNA KCNQ1OT1 could activate the Caspase-1 pathway through the regulation of miRNA-214, thereby inducing cataract formation. However, miRNA-26a and miRNA-26b could negatively regulate the Jagged-1/Notch signaling pathway to inhibit the formation of cataract, as demonstrated in the study by Chen et al [12].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-124 Prevents H<sub>2</sub>O<sub>2</sub>-Induced Apoptosis and Oxidative Stress in Human Lens Epithelial Cells via Inhibition of the NF-κB Signaling Pathway

Gu¹

2018

Pharmacology

View full text Add to dashboard Cite

Aim: To investigate the regulation of microRNA-124 (miRNA-124) on NF-κB pathway from H₂O₂-induced apoptosis and oxidative stress in human lens epithelial cells (hLEC). Methods: The MTT (3-[4, 5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to detect hLEC viability. HLECs were divided into Blank, H₂O₂, mimics (miRNA-124 mimics) + H₂O₂, NC+ H₂O₂, pyrrolidine dithiocarbamate (PDTC; NF-κB signaling pathway inhibitor) + H₂O₂, and inhibitors (miRNA-124 inhibitors) + PDTC + H₂O₂ groups. Quantitative real-time polymerase chain reaction and Western blot were employed to detect mRNA and protein expressions, Dichloro-dihydro-fluorescein diacetate to measure reactive oxygen species (ROS) production, and AnnexinV-FITC/PI staining to determine cell apoptosis. The mitochondrial membrane potential (MMP) was detected by fluorescence probe JC-1. Results: The H₂O₂-induced hLEC showed reductions in cell viability with decreased miRNA-124 but increased p-p65 in a dose-/time-dependent manner. Furthermore, ROS production, malondialdehyde content, Bax and Caspase-3 expressions, and cell apoptosis were elevated in H₂O_2-induced hLEC, whereas the activities of superoxide dismutase and glutathione peroxidase, Bcl-2 expression, MMP, as well as the mitochondrial energy metabolism genes were reduced. Additionally, miRNA-124 mimics and PDTC both decreased the p-p65 and reversed the cytotoxicity in H₂O₂-induced hLEC. Conclusion: MiRNA-124 prevents H₂O₂-induced oxidative stress and apoptosis in hLEC through suppressing the activation of the NF-κB pathway.

show abstract

Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway

Cited by 63 publications

References 34 publications

LncRNA KCNQ1OT1 Mediates Pyroptosis in Diabetic Cardiomyopathy

LncRNA KCNQ1OT1 Mediates Pyroptosis in Diabetic Cardiomyopathy

Long Non-Coding RNA H19 Regulates Human Lens Epithelial Cells Function

MicroRNA-124 Prevents H<sub>2</sub>O<sub>2</sub>-Induced Apoptosis and Oxidative Stress in Human Lens Epithelial Cells via Inhibition of the NF-κB Signaling Pathway

Contact Info

Product

Resources

About