Transcriptomic analysis of the role of RasGEF1B circular RNA in the TLR4/LPS pathway

Ng, Wei Lun; Marinov, Georgi K.; Chin, Yoon Ming; Lim, Yun Mook; Kwee, Chee

doi:10.1038/s41598-017-12550-w

Cited by 29 publications

(18 citation statements)

References 31 publications

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“…LPS activates the Ras signaling pathway by binding to TLR4 (Ng et al, 2017), resulting in increased production of several inflammatory mediators and effector molecules in macrophages (Kim and Kim, 2005). We showed that colonic LPS levels in the DSS group were significantly higher than those in the control group (p < 0.01, Figure 4).…”

Section: Huangqin Decoction Suppressed the Ras Signaling Pathway Thromentioning

confidence: 78%

Anti-Inflammatory Effects of Huangqin Decoction on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice Through Regulation of the Gut Microbiota and Suppression of the Ras-PI3K-Akt-HIF-1α and NF-κB Pathways

Luo

et al. 2020

Front. Pharmacol.

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Objective: Huangqin decoction (HQD), a classical traditional Chinese medicinal formula, has been commonly used to treat gastrointestinal diseases for thousands of years. We investigated the anti-inflammatory effects and underlying mechanisms of HQD on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC).Methods: Experimental mice were given 3% DSS, and HQD (2.275, 4.55, and 9.1 g/kg), or mesalazine (ME, 200 mg/kg) orally for 7 days. Body weight loss, disease activity index (DAI), colon length, histology, and levels of inflammatory cytokines were measured to evaluate the effects of HQD on colitis. The effects of HQD on the Ras-phosphoinositide-3kinase (PI3K)-Akt-hypoxia inducible factor 1 alpha (HIF-1a) and nuclear factor-kappa B (NF-kB) pathways were evaluated by Western blot analysis. In addition, the gut microbiota was characterized using high-throughput Illumina MiSeq sequencing. Results:The results showed that HQD significantly reduced the body weight loss, ameliorated DAI, restored colon length, and improved the intestinal epithelial cell barrier in mice with DSS-induced colitis. The messenger RNA (mRNA) expression levels of inflammatory mediators were decreased following HQD treatment. Furthermore, the Ras-PI3K-Akt-HIF-1a and NF-kB pathways were significantly inhibited by HQD. Finally, treatment with HQD resulted in recovery of gut microbiota diversity.Conclusions: HQD ameliorates DSS-induced colitis through regulation of the gut microbiota, and suppression of Ras-PI3K-Akt-HIF-1a and NF-kB pathways. Our results suggested that HQD may be a potential candidate for treatment of UC.GRAPHICAL ABSTRACT | This study demonstrated that supplementation of Huangqin decoction (HQD) attenuated dextran sulfate sodium (DSS)-induced ulcerative colitis by regulating the gut microbiota and suppressing Ras-PI3K-Akt-HIF-1a and NF-kB pathways in mice.

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Section: Huangqin Decoction Suppressed the Ras Signaling Pathway Thromentioning

confidence: 78%

Anti-Inflammatory Effects of Huangqin Decoction on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice Through Regulation of the Gut Microbiota and Suppression of the Ras-PI3K-Akt-HIF-1α and NF-κB Pathways

Luo

et al. 2020

Front. Pharmacol.

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“…For instance, circ-RasGEF1B positively regulates the expression of intercellular adhesion molecule 1 ( ICAM-1 ), which is an adhesion protein that anchors on the surface of the cell membranes of macrophages and promotes cell-cell interactions during antigen presentation by modulating the stability of mature ICAM-1 mRNA 75. Moreover, circ-RasGEF1B is necessary for the proper activation of macrophages exposed to lipopolysaccharide (LPS) 76. Holdt et al confirmed that circ-ANRIL could associate with pescadillo ribosomal biogenesis factor 1 (PES1) to impede exonuclease-mediated pre-rRNA generation and ribosome formation, thus elevating apoptosis and suppressing proliferation in macrophages by inducing the expression of Tp53 77.…”

Section: Identification Biogenesis and Functions Of Circrnasmentioning

confidence: 99%

Circular RNAs in immune responses and immune diseases

et al. 2019

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Circular RNAs (circRNAs) are novel clusters of endogenous noncoding RNAs (ncRNAs) that are widely expressed in eukaryotic cells. In contrast to the generation of linear RNA transcripts, circRNAs undergo a “back-splicing” process to form a continuous, covalently closed, stable loop structure without 5ʹ or 3ʹ polarities and poly (A) tails during posttranscriptional modification. Due to the widespread availability of several technologies, especially high-throughput RNA sequencing, numerous circRNAs have been discovered not only in mammals but also in plants and insects. Notably, due to their abilities to serve as microRNA (miRNA) “sponges”, miRNA “reservoirs”, regulate gene expression and encode proteins, circRNAs participate in the development and progression of different immune responses and immune diseases by enriching various forms of epigenetic modification. CircRNAs have been demonstrated to be expressed in a tissue-specific and pathogenesis-related manner during the occurrence of multiple immune diseases. Additionally, because of their circular configurations, expression in blood and peripheral tissues and coexistence with exosomes, circRNAs show inherent conservation along with environmental resistance stability and may be regarded as potential biomarkers or therapeutic targets for some immune diseases. In this review, we summarize the characteristics, functions and mechanisms of circRNAs and their involvement in immune responses and diseases. Although our knowledge of circRNAs remains preliminary, this field is worthy of deeper exploration and greater research efforts.

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“…Circular RNAs (circRNAs) are a novel class of RNAs that participate in several physiological and pathological processes (Liu et al, 2017 ; Ng et al, 2017 ). Growing evidence has suggested that many circRNAs can function as competing endogenous (ceRNAs) RNAs to block the functions of their target microRNAs (miRNAs) by binding target miRNAs, a mechanism called miRNA sponging (Kulcheski et al, 2016 ; Rong et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Plasma Circular RNAs hsa_circ_0001953 and hsa_circ_0009024 as Diagnostic Biomarkers for Active Tuberculosis

Qing

Peng

et al. 2018

Front. Microbiol.

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Recent studies have demonstrated that circular RNAs (circRNAs) could serve as potential molecular markers for disease diagnosis; however, little is known about their diagnostic value in active tuberculosis (TB). This study first performed a microarray screening of circRNA changes in plasma samples from 3 patients with active pulmonary TB and 3 healthy controls. Then, candidate circRNAs were selected for validation on a quantitative real-time PCR system. Of the 61 differentially expressed circRNAs recorded, 43 and 18 were upregulated and downregulated in the TB group, respectively. Validation assays demonstrated that plasma levels of 6 circRNAs, including hsa_circ_0009024, hsa_circ_0001953, hsa_circ_0008297, hsa_circ_0003528, hsa_circ_0003524 and hsa_circ_0015879 were remarkably increased in TB patients. Plasma levels of hsa_circ_0001953 and hsa_circ_0009024 were correlated with TB severity. Next, hsa_circ_0001953 and hsa_circ_0009024 were assessed in an independent cohort consisting of 120 TB patients and 100 control individuals. An area under the receiver operating characteristic (ROC) curve of 0.915 (95% confidence interval 0.880-0.951; P < 0.001) was obtained for detecting TB, with hsa_circ_0001953 and hsa_circ_0009024 used in combination. Additionally, plasma levels of hsa_circ_0001953 and hsa_circ_0009024 were reduced significantly in patients after treatment (P < 0.001). The present findings indicate that the circRNAs hsa_circ_0001953 and hsa_circ_0009024 may represent novel plasma biomarkers for active TB diagnosis.

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Transcriptomic analysis of the role of RasGEF1B circular RNA in the TLR4/LPS pathway

Cited by 29 publications

References 31 publications

Anti-Inflammatory Effects of Huangqin Decoction on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice Through Regulation of the Gut Microbiota and Suppression of the Ras-PI3K-Akt-HIF-1α and NF-κB Pathways

Anti-Inflammatory Effects of Huangqin Decoction on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice Through Regulation of the Gut Microbiota and Suppression of the Ras-PI3K-Akt-HIF-1α and NF-κB Pathways

Circular RNAs in immune responses and immune diseases

Plasma Circular RNAs hsa_circ_0001953 and hsa_circ_0009024 as Diagnostic Biomarkers for Active Tuberculosis

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