YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin II-induced atrial fibrillation by modulating miR-384b/CACNA1C axis

Shen, Caijie; Kong, Bin; Liu, Yü; Xiong, Liang; Shuai, Wei; Wang, Guangji; Quan, Dajun; Huang, He

doi:10.1016/j.bbrc.2018.09.064

Cited by 51 publications

(29 citation statements)

References 26 publications

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“…Several studies also have suggested upstream signaling pathways regulating KCNQ1OT1 in different disease paradigms. Shen et al reported that YY1 up-regulated KCNQ1OT1 and contributed to atrial fibrillation [49]. Sunamura et al showed that β-catenin promoted the development of colorectal cancer by directly up-regulating the transcription of KCNQ1OT1 [50].…”

Section: Discussionmentioning

confidence: 99%

LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of prostate cancer via up-regulating PD-L1

Chen

Liu

et al. 2020

Cancer Cell Int

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Background: We focused on the KCNQ1OT1/miR-15a/PD-L1 axis and explored its significance in regulating immune evasion and malignant behaviors of prostate cancer (PC) cells. Methods: The expression levels of KCNQ1OT1, miR-15a, PD-L1, and CD8 in cells or tissues were examined by RT-qPCR, western blot or immunohistochemistry (IHC) assays. The direct regulations between KCNQ1OT1, miR-15a and PD-L1 were validated by luciferase reporter assay. PC cells were co-cultured with CD8 + T cells to study the immune evasion. Proliferation, apoptosis, migration and invasion abilities were detected by MTT, flow cytometry, wound healing and Transwell assays, respectively. The cytotoxicity of CD8 + T cells was determined by LDH cytotoxicity Kit. Epithelial-mesenchymal transition (EMT) and Ras/ERK signaling markers were evaluated by western blot. Results: KCNQ1OT1, PD-L1 and CD8 were increased, while miR-15a was decreased in PC tissues. MiR-15a directly bound to the 3′-UTR of PD-L1 and inhibited the expression of PD-L1. Overexpressing miR-15a in PC cells was sufficient to promote cytotoxicity and proliferation, while inhibit apoptosis of CD8 + T cells, and also suppressed viability, migration, invasion and EMT while promoted apoptosis of PC cells. The above anti-tumor effects of miR-15a were reversed by overexpressing PD-L1. KCNQ1OT1 sponged miR-15a and released its inhibition on PD-L1. Functionally, KCNQ1OT1 in PC cells was essential for suppressing the cytotoxicity of CD8 + T cells and maintaining multiple malignant phenotypes of PC cells. The Ras/ERK signaling was suppressed after overexpressing miR-15a or knocking down KCNQ1OT1. Conclusions: LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of PC via up-regulating PD-L1.

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Section: Discussionmentioning

confidence: 99%

LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of prostate cancer via up-regulating PD-L1

Chen

Liu

et al. 2020

Cancer Cell Int

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“…For instance, lncRNA AK055347 is upregulated in AF patients and regulates mitochondrial energy production in myocardiocytes (Chen et al 2016). A more recent study revealed that lncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1) is upregulated in Ang-II-induced AF mice hearts and promotes Ang-II-induced AF by acting as a sponge for miR-384b to facilitate CACNA1C expression (Shen et al 2018). Nevertheless, the exact role of lncRNAs in AF still need to be further elucidated.…”

Section: Discussionmentioning

confidence: 99%

LncRNA PVT1 regulates atrial fibrosis via miR-128-3p-SP1-TGF-β1-Smad axis in atrial fibrillation

Cao

Ding

et al. 2019

Mol Med

122

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Background: Long non-coding RNAs (lncRNA) plasmacytoma variant translocation 1 (PVT1) has been shown to be associated with liver fibrosis. Nevertheless, the role of PVT1 in atrial fibrosis remains undefined. This study aims to elucidate the pathophysiological role of lncRNA PVT1 in the regulation of atrial fibrosis and to explore the underlying mechanism. Methods: Expression of PVT1, miR-128-sp, and Sp1 were examined in human atrial muscle tissues and angiotensin-II (Ang-II)-induced human atrial fibroblasts. Furthermore, the role of PVT1 in regulating atrial fibrosis in Ang-II-treated human atrial fibroblasts and Ang-II-induced atrial fibrosis in mice was investigated. Moreover, the interaction among PVT1, miR-128-3p, and Sp1 were examined using bioinformatics, expression correlation analysis, gain-or loss-offunction assays, RIP assays, and luciferase reporter assays. The involvement of transforming growth factor beta 1 (TGF-β1)/Smad pathway in this process was also explored. Results: PVT1 was increased in atrial muscle tissues from AF patients and positively with collagen I and collagen III. In vitro assay revealed that PVT1 overexpression facilitated the Ang-II-induced atrial fibroblasts proliferation, collagen production, and TGF-β1/Smad signaling activation, whereas PVT1 knockdown caused the opposite effect. In vivo assay further confirmed that PVT1 knockdown attenuated the Ang-II-induced mouse atrial fibrosis. Mechanically, PVT1 acted as a sponge for miR-128-3p to facilitate Sp1 expression, thereby activating the TGF-β1/Smad signaling pathway. Conclusion: LncRNA PVT1 promotes atrial fibrosis via miR-128-3p-SP1-TGF-β1-Smad axis in atrial fibrillation.

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“…At present, assays of the functional role of lncRNAs have only been reported in experimental animal models or in in vitro assays. Several of these studied reported a functional role of lncRNAs modulating fibrosis [ 188 , 189 , 190 , 191 ], ion channel function [ 192 , 193 , 194 , 195 , 196 , 197 ], and energy metabolism [ 198 ] as detailed below.…”

Section: Epigenetics Of Atrial Fibrillationmentioning

confidence: 99%

“…Several reports provided evidence on the functional role of lncRNAs modulating the cardiac electrophysiological properties in AF, particularly those related to calcium regulation and handling. Shen et al [ 194 ] reported that KCNQ1OT1 is up-regulated in AngII-treated mice as well as in an experimental AF mouse model. The authors demonstrate that KCNQ1OT1 regulates CACNA1C by sponging miR-384.…”

Section: Epigenetics Of Atrial Fibrillationmentioning

confidence: 99%

Genetics and Epigenetics of Atrial Fibrillation

Lozano-Velasco

Franco

Aránega

et al. 2020

IJMS

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Atrial fibrillation (AF) is known to be the most common supraventricular arrhythmia affecting up to 1% of the general population. Its prevalence exponentially increases with age and could reach up to 8% in the elderly population. The management of AF is a complex issue that is addressed by extensive ongoing basic and clinical research. AF centers around different types of disturbances, including ion channel dysfunction, Ca2+-handling abnormalities, and structural remodeling. Genome-wide association studies (GWAS) have uncovered over 100 genetic loci associated with AF. Most of these loci point to ion channels, distinct cardiac-enriched transcription factors, as well as to other regulatory genes. Recently, the discovery of post-transcriptional regulatory mechanisms, involving non-coding RNAs (especially microRNAs), DNA methylation, and histone modification, has allowed to decipher how a normal heart develops and which modifications are involved in reshaping the processes leading to arrhythmias. This review aims to provide a current state of the field regarding the identification and functional characterization of AF-related epigenetic regulatory networks

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YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin II-induced atrial fibrillation by modulating miR-384b/CACNA1C axis

Cited by 51 publications

References 26 publications

LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of prostate cancer via up-regulating PD-L1

LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of prostate cancer via up-regulating PD-L1

LncRNA PVT1 regulates atrial fibrosis via miR-128-3p-SP1-TGF-β1-Smad axis in atrial fibrillation

Genetics and Epigenetics of Atrial Fibrillation

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