Silica‐induced initiation of circular
            <i>ZC3H4</i>
            RNA/ZC3H4 pathway promotes the pulmonary macrophage activation

Yang, Xiyue; Wang, Jing; Zhou, Zewei; Jiang, Rong; Huang, Jie; Chen, Lulu; Cao, Zhouli; Han, Chunchun; Han, Bing; Cheng, Yusi; Chao, Jie

doi:10.1096/fj.201701118r

Cited by 93 publications

(76 citation statements)

References 47 publications

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“…Elevated level of macrophages can infiltrate in the inflamed synovium tissue and cause inflammatory lesions and joint damage in RA 3 . Some circRNAs are reported to be specifically expressed in macrophages and affect their differentiation, infiltration, activation, and function in particular tissues [28][29][30] . There are different expression patterns of circRNAs in diverse polarized macrophages primarily including pro-inflammatory M1 and antiinflammatory M2 macrophages 28 .…”

Section: Discussionmentioning

confidence: 99%

CircRNA_09505 aggravates inflammation and joint damage in collagen-induced arthritis mice via miR-6089/AKT1/NF-κB axis

et al. 2020

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A number of circular RNAs (circRNAs) have been implicated in rheumatoid arthritis (RA) pathogenesis; however, little is known about their function and hidden molecular mechanism in immune and inflammation regulation. We investigated the role and the underlying mechanism of circRNA_09505 in RA in this study. Real-time PCR and fluorescence in situ hybridization (FISH) are adopted to estimate the quantitative expression and localization of circRNA_09505 in macrophages. The altering effect of circRNA_09505 on inflammation is investigated in vitro and in vivo by use of macrophage cell models and collagen-induced arthritis (CIA) mice. Luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) are used to confirm the circRNA_09505/miR-6089 ceRNA network predicted by bioinformatics analysis. Compared with controls, the expression of circRNA_09505 is upregulated in peripheral blood mononuclear cells (PBMCs) from patients with RA. The proliferation and cell cycle are significantly promoted when circRNA_09505 is upregulated in macrophages, whereas knockdown of circRNA_09505 inhibits macrophage proliferation and cell- cycle progression. Besides, circRNA_09505 can act as a miRNA sponge for miR-6089 in macrophages, and promote the production of TNF-α, IL-6, and IL-12 through ceRNA mechanism. Moreover, AKT1 is a direct target of miR-6089. CircRNA_09505 can promote AKT1 expression by acting as a miR-6089 sponge via IκBα/NF-κB signaling pathway in macrophages. Most interestingly, knockdown of circRNA_09505 significantly alleviates arthritis and inflammation in vivo in CIA mice. These data support the hypothesis that circRNA_09505 can function as a miR-6089 sponge and regulate inflammation via miR-6089/AKT1/NF-κB axis in CIA mice.

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Section: Discussionmentioning

confidence: 99%

CircRNA_09505 aggravates inflammation and joint damage in collagen-induced arthritis mice via miR-6089/AKT1/NF-κB axis

et al. 2020

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“…Previous studies have shown that circRNAs and lncRNAs can participate in post-transcriptional regulation through the competitive binding of miRNAs. 18 Some studies have shown that circRNAs can bind to many miRNAs to participate in normal growth and development. 19 However, only a few bovine circRNAs, such as circSNX29, have been shown to play a key role in growth.…”

Section: Discussionmentioning

confidence: 99%

circFLT1 and lncCCPG1 Sponges miR-93 to Regulate the Proliferation and Differentiation of Adipocytes by Promoting lncSLC30A9 Expression

Kang

Zhang

Jiang

et al. 2020

Molecular Therapy - Nucleic Acids

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Although many circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) have been discovered in adipocytes, their precise functions and molecular mechanisms remain poorly understood. Based on existing circRNA and lncRNA sequencing data of bovine adipocytes, we screened for the differential expression of circFLT1 and lncCCPG1 in preadipocytes and adipocytes and further analyzed their function and regulation during adipogenesis. The overexpression of circFLT1 and lncCCPG1 together facilitated adipocyte differentiation and suppressed proliferation. Computationally, the RNA hybrid showed that circFLT1 and lncCCPG1 had multiple potential binding sites with miR-93. Additionally, luciferase reporting experiments verified that circFLT1 and lncCCPG1 may interact with miR-93. We also demonstrated that overexpressed miR-93 effectively suppresses the expression of lncSLC30A9 . Signaling pathway enrichment analysis, luciferase activity assay, and expression analysis revealed that lncSLC30A9 inhibits proliferation by inhibiting the expression of AKT protein and promotes differentiation by recruiting the FOS protein to the promoter of peroxisome proliferator-activated receptor gamma ( PPARG ). In sum, our results elucidate the regulatory mechanisms of circFLT1 and lncCCPG1 as miR-93 sponges in bovine adipocytes.

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“…Macrophages subtypes (M1-type macrophages and M2-type macrophages) play a key role in the induction and regulation of specific immune responses and the development and recovery of disease. It have been indicated that circZC3H4 take part in SiO 2 induced macrophage activation through HECTD1/ZC3H12A dependent ubiquitin-proteasome pathway (43). Circ-RasGEF1B is necessary for macrophage activation after exposure to lipopolysaccharide (LPS) (44).…”

Section: Circrnas In Immune Regulationmentioning

confidence: 99%

The Role of Circular RNAs in Immune-Related Diseases

Xie

Zhang

et al. 2020

Front. Immunol.

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Circular RNAs (circRNAs) are a novel class of RNAs with a covalently closed loop structure without a 3 ′ polyadenylation [poly-(A)] tail or a 5 ′ cap. They used to be considered as the occasional and useless products of RNA splicing errors because they could not be detected by traditional RNA sequencing technology. Benefiting from the development of specific biochemical and computational approaches, researchers showed that circRNAs are universally expressed and functional. Further studies have revealed their important functions regarding regulating gene expression at the transcriptional and post-transcriptional levels. These functions include acting as microRNA (miRNA) sponges, binding to RNA-binding proteins (RBPs), acting as transcriptional regulatory factors, and serving as translation templates. The advances in circRNA research has opened researchers' eyes to a new area of research on the roles of circRNAs in the pathogenesis of various diseases, especially at the immune level because of the close relationship between circRNAs and the immune response. Emerging research indicates that circRNAs could act as potential biomarkers related to diagnosis, therapeutic effects, and prognosis, and they may be effective therapeutic targets in immunological disorders, including certain diseases that are currently difficult to treat.

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Silica‐induced initiation of circular ZC3H4 RNA/ZC3H4 pathway promotes the pulmonary macrophage activation

Cited by 93 publications

References 47 publications

CircRNA_09505 aggravates inflammation and joint damage in collagen-induced arthritis mice via miR-6089/AKT1/NF-κB axis

CircRNA_09505 aggravates inflammation and joint damage in collagen-induced arthritis mice via miR-6089/AKT1/NF-κB axis

circFLT1 and lncCCPG1 Sponges miR-93 to Regulate the Proliferation and Differentiation of Adipocytes by Promoting lncSLC30A9 Expression

The Role of Circular RNAs in Immune-Related Diseases

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