Circular RNA circHIPK3 modulates the proliferation of airway smooth muscle cells by miR-326/STIM1 axis

Lin, Junling; Feng, Xiaokai; Zhang, Jun

doi:10.1016/j.lfs.2020.117835

Cited by 30 publications

(21 citation statements)

References 27 publications

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“…Circular RNAs (circRNAs) are a unique class of noncoding RNAs consisting of covalently closed, single‐stranded transcripts that are highly conserved and stable because of their lack of accessible ends 8 . Several circRNAs have been shown to regulate physiological and pathological processes, including autophagy, proliferation, migration, and invasion 9‐11 . In this study, a novel circRNA, hsa_circ_0003489, was found located at the gene for cyclin‐dependent kinase 8 (CDK8), a key transcriptional regulator of cell cycle progression, and is involved in the regulation of autophagy.…”

Section: Introductionmentioning

confidence: 99%

CircCDK8 regulates osteogenic differentiation and apoptosis of PDLSCs by inducing ER stress/autophagy during hypoxia

Zheng

Zhu

et al. 2020

Annals of the New York Academy of Sciences

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Mounting evidence indicates that circular RNAs (circRNAs) have essential roles in several diseases, including periodontitis. Periodontal ligament stem cells (PDLSCs) exhibit potential for treating periodontitis accompanied by hypoxia. However, it is unclear how circRNA affects the osteogenesis of PDLSCs under hypoxia. In this study, a novel circRNA, hsa_circ_0003489, was found located at the gene for cyclin‐dependent kinase 8 (CDK8) and referred to as circCDK8. The expression levels of circCDK8 and hypoxia‐inducible factor‐1α were significantly increased in periodontitis tissues, and the expression of circCDK8 was further confirmed in a hypoxia model using cobalt chloride (CoCl2). Interestingly, the results showed that the expression levels of osteoblast markers (RUNX2, ALP, OCN, and COL1A1) were increased in CoCl2‐treated PDLSCs at 6 and 12 h, but decreased at 24, 48, and 72 h. On the basis of bioinformatics and functional experiments, CoCl2 also induced endoplasmic reticulum stress, autophagy, and apoptosis of PDLSCs; the inhibition of autophagy promoted the osteogenic differentiation of CoCl2‐treated PDLSCs. Furthermore, circCDK8 overexpression induced autophagy and apoptosis through mTOR signaling, and circCDK8 silencing reversed the inhibitory effects of CoCl2 on osteogenic differentiation of PDLSCs. In conclusion, our results indicate that circCDK8 represses the osteogenic differentiation of PDLSCs by triggering autophagy activation in a hypoxic microenvironment. CircCDK8 could be a new therapeutic target of periodontitis.

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Section: Introductionmentioning

confidence: 99%

CircCDK8 regulates osteogenic differentiation and apoptosis of PDLSCs by inducing ER stress/autophagy during hypoxia

Zheng

Zhu

et al. 2020

Annals of the New York Academy of Sciences

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“…As an ecRNA, circHIPK3 can be transported into the cytoplasm and is mostly cytoplasm-located. CircHIPK3 is widely expressed in various tissues, such as the heart, lung and colon (26), consistent with its roles in CVD (32,(43)(44)(45)(46), cancers (12,27,28,47), and neuronal diseases (48,49). CircHIPK3 mainly functions through sponging miRNAs (32,34,43,44,50).…”

Section: Biogenesis and Mechanisms Of Actions Of Circhipk3mentioning

confidence: 74%

CircHIPK3 Plays Vital Roles in Cardiovascular Disease

Zhang

Yin

et al. 2021

Front. Cardiovasc. Med.

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Circular RNAs (circRNAs) are covalently closed RNAs that function in various physiological and pathological processes. CircRNAs are widely involved in the development of cardiovascular disease (CVD), one of the leading causes of morbidity and mortality worldwide. CircHIPK3 is generated from the second exon of the HIPK3 gene, a corepressor of homeodomain transcription factors. As an exonic circRNA (ecRNA), circHIPK3 is produced through intron-pairing driven circularization facilitated by Alu elements. In the past 5 years, a growing number of studies have revealed the multifunctional roles of circHIPK3 in different diseases, such as cancer and CVD. CircHIPK3 mainly participates in CVD pathogenesis through interacting with miRNAs. This paper summarizes the current literature on the biogenesis and functions of circHIPK3, elucidates the role of circHIPK3 in different CVD patterns, and explores future perspectives.

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“… 21 Lin et al exhibited that circHIPK3 contributed to proliferation and migration of airway smooth muscle cells in the development of asthma via the miR-326/STIM1 axis. 22 The researches of COPD have revealed that circBbs9 enhanced lung inflammation via targeting the miR-30e-5p/Adar pathway, 23 and hsa_circRNA_0008672 promoted the pathogenesis of COPD via acting on the miR-1265/MAPK1 axis. 24 …”

Section: Discussionmentioning

confidence: 99%

Circ-HACE1 Aggravates Cigarette Smoke Extract-Induced Injury in Human Bronchial Epithelial Cells via Regulating Toll-Like Receptor 4 by Sponging miR-485-3p

Zhou

Cao²,

Chai³

et al. 2021

COPD

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Background Smoking is the most common cause of chronic obstructive pulmonary disease (COPD), and the early diagnosis for COPD remains poor. Exploring the molecular mechanism and finding feasible biomarkers will be beneficial for clinical management of COPD. Circular RNAs (circRNAs) are noncoding RNAs that act as miRNA sponges to regulate the expression levels of genes, leading to the changes of cellular phenotypes and disease progression. CircRNA HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (circ-HACE1) was abnormally expressed after the induction of cigarette smoke extract (CSE) in cell model. This study was performed to explore its function and mechanism in COPD. Methods Circ-HACE1, microRNA-485-3p (miR-485-3p) and toll-like receptor 4 (TLR4) detection was performed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis/cell cycle were respectively examined using cell counting kit-8 (CCK-8) and flow cytometry. Inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA). Oxidative stress was evaluated through the measurement of malondialdehyde (MDA) and superoxide dismutase (SOD). The target binding analysis was conducted via dual-luciferase reporter assay. Western blot was employed for protein expression detection of TLR4. Results Circ-HACE1 was overexpressed in smokers or smokers with COPD and CSE upregulated circ-HACE1 expression in 16HBE cells. Knockdown of circ-HACE1 attenuated CSE-stimulated cell viability and cell cycle repression, as well as the enhancement of cell apoptosis, inflammatory response and oxidative stress. MiR-485-3p was a target of circ-HACE1. Circ-HACE1 regulated CSE-induced cell injury via targeting miR-485-3p. TLR4 was a downstream target of miR-485-3p, and miR-485-3p inhibited the CSE-induced cell damages by directly downregulating the level of TLR4. Circ-HACE1/miR-485-3p regulated TLR4 expression in CSE-treated 16HBE cells, and TLR4 overexpression also reversed all effects of si-circ-HACE1 on CSE-treated 16HBE cells. Conclusion These findings elucidated that circ-HACE1 contributed to the CSE-induced cell damages in COPD cell models via regulating TLR4 by acting as the sponge of miR-485-3p.

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Circular RNA circHIPK3 modulates the proliferation of airway smooth muscle cells by miR-326/STIM1 axis

Cited by 30 publications

References 27 publications

CircCDK8 regulates osteogenic differentiation and apoptosis of PDLSCs by inducing ER stress/autophagy during hypoxia

CircCDK8 regulates osteogenic differentiation and apoptosis of PDLSCs by inducing ER stress/autophagy during hypoxia

CircHIPK3 Plays Vital Roles in Cardiovascular Disease

Circ-HACE1 Aggravates Cigarette Smoke Extract-Induced Injury in Human Bronchial Epithelial Cells via Regulating Toll-Like Receptor 4 by Sponging miR-485-3p

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