CircNFIC Balances Inflammation and Apoptosis by Sponging miR-30e-3p and Regulating DENND1B Expression

Chen, Yangfeng; Wang, Zhijun; Chen, Xiaolan; Peng, Xi; Nie, Qinghua

doi:10.3390/genes12111829

Cited by 12 publications

(4 citation statements)

References 68 publications

(83 reference statements)

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“…Both RNA and protein levels of IL-1β decreased following miR-30e-3p transfection, and direct interaction of miR-30e-3p -IL-1β was identified by 3'UTR luciferase assay. Similar to our findings, Chen et al showed that miR-30e-3p is a part of inflammation and apoptosis regulator complex with CircNFIC and DENND1B and regulates IL-1β secretion in chicken macrophage cell lines [27]. Also, the role of miR-30e-3p on drug resistance was reported in different cancer types [28,29].…”

Section: Discussionsupporting

confidence: 90%

Dysregulation of miRNA-30e-3p targeting IL-1β in an international cohort of systemic autoinflammatory disease patients

et al. 2023

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Autoinflammation is the standard mechanism seen in systemic autoinflammatory disease (SAID) patients. This study aimed to investigate the effect of a candidate miRNA, miR-30e-3p, which was identified in our previous study, on the autoinflammation phenotype seen in SAID patients and to analyze its expression in a larger group of European SAID patients. We examined the potential anti-inflammatory effect of miR-30e-3p, which we had defined as one of the differentially expressed miRNAs in microarray analysis involved in inflammation-related pathways. This study validated our previous microarray results of miR-30e-3p in a cohort involving European SAID patients. We performed cell culture transfection assays for miR-30e-3p. Then, in transfected cells, we analyzed expression levels of pro-inflammatory genes; IL-1β, TNF-α, TGF-β, and MEFV. We also performed functional experiments, caspase-1 activation by fluorometric assay kit, apoptosis assay by flow cytometry, and cell migration assays by wound healing and filter system to understand the possible effect of miR-30e-3p on inflammation. Following these functional assays, 3'UTR luciferase activity assay and western blotting were carried out to identify the target gene of the aforementioned miRNA. MiR-30e-3p was decreased in severe European SAID patients like the Turkish patients. The functional assays associated with inflammation suggested that miR-30e-3p has an anti-inflammatory effect. 3'UTR luciferase activity assay demonstrated that miR-30e-3p directly binds to interleukin-1-beta (IL-1β), one of the critical molecules of inflammatory pathways, and reduces both RNA and protein levels of IL-1β. miR-30e-3p, which has been associated with IL-1β, a principal component of inflammation, might be of potential diagnostic and therapeutic value for SAIDs. Key Messages• miR-30e-3p, which targets IL-1β, could have a role in the pathogenesis of SAID patients.• miR-30e-3p has a role in regulating inflammatory pathways like migration, caspase-1 activation.• miR-30e-3p has the potential to be used for future diagnostic and therapeutic approaches.

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Section: Discussionsupporting

confidence: 90%

Dysregulation of miRNA-30e-3p targeting IL-1β in an international cohort of systemic autoinflammatory disease patients

et al. 2023

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“…In the nucleus, circRNAs combine with RNA polymerase II to regulate the transcriptional activity [ 26 ]. Alternatively, in the cytoplasm, circRNAs act as molecular sponges to bind with specific miRNA to promote the function of target genes [ 27 , 28 , 29 , 30 , 31 , 32 ]. For example, it has been demonstrated that circPTPN4 can stimulate NAMPT expression by sponging miR-499-3P in the cytoplasm and acting as a competing endogenous RNA [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

CircPLXNA2 Affects the Proliferation and Apoptosis of Myoblast through circPLXNA2/gga-miR-12207-5P/MDM4 Axis

Dong

Xing

Liu

et al. 2023

IJMS

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CircRNAs are newly identified special endogenous RNA molecules that covalently close a loop by back-splicing with pre-mRNA. In the cytoplasm, circRNAs would act as molecular sponges to bind with specific miRNA to promote the expression of target genes. However, knowledge of circRNA functional alternation in skeletal myogenesis is still in its infancy. In this study, we identified a circRNA–miRNA–mRNA interaction network in which the axis may be implicated in the progression of chicken primary myoblasts’ (CPMs) myogenesis by multi-omics (i.e., circRNA-seq and ribo-seq). In total, 314 circRNA–miRNA–mRNA regulatory axes containing 66 circRNAs, 70 miRNAs, and 24 mRNAs that may be relevant to myogenesis were collected. With these, the circPLXNA2-gga-miR-12207-5P-MDM4 axis aroused our research interest. The circPLXNA2 is highly differentially expressed during differentiation versus proliferation. It was demonstrated that circPLXNA2 inhibited the process of apoptosis while at the same time stimulating cell proliferation. Furthermore, we demonstrated that circPLXNA2 could inhibit the repression of gga-miR-12207-5p to MDM4 by directing binding to gga-miR-12207-5p, thereby restoring MDM4 expression. In conclusion, circPLXNA2 could function as a competing endogenous RNA (ceRNA) to recover the function of MDM4 by directing binding to gga-miR-12207-5p, thereby regulating the myogenesis.

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“…Its downregulation should indicate higher expression levels of the target gene CAMK2A, which, in turn, would activate the mentioned functions. Other dysregulated miRNAs in common such as miR-126-5p, miR-30e-3p and miR-186-5p have been related with the inflammatory signal [21][22][23] , pointing towards an active response to the vaccines and the adjuvant in spleen. There were few miRNAs differentially expressed after aluminium adjuvant-only treatment, and only four were exclusive to that treatment, even if we did not find any DE miRNA between both treatment groups.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of miRNAs in spleens of sheep subjected to repetitive vaccination

Varela-Martínez

Bilbao-Arribas

Abendaño

et al. 2023

Sci Rep

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Accumulative evidence has shown that short non-coding RNAs such as miRNAs can regulate the innate and adaptive immune responses. Aluminium hydroxide is a commonly used adjuvant in human and veterinary vaccines. Despite its extended use, its mechanism of action is not fully understood and very few in vivo studies have been done to enhance understanding at the molecular level. In this work, we took advantage of a previous long-term experiment in which lambs were exposed to three different treatments by parallel subcutaneous inoculations with aluminium-containing commercial vaccines, an equivalent dose of aluminium or mock injections. Spleen samples were used for miRNA-seq. A total of 46 and 16 miRNAs were found differentially expressed when animals inoculated with commercial vaccines or the adjuvant alone were compared with control animals, respectively. Some miRNAs previously related to macrophage polarization were found dysregulated exclusively by the commercial vaccine treatment but not in the aluminium inoculated animals. The dysregulated miRNAs in vaccine group let-7b-5p, miR-29a-3p, miR-27a and miR-101-3p are candidates for further research, since they may play key roles in the immune response induced by aluminium adjuvants added to vaccines. Finally, protein–protein interaction network analysis points towards leucocyte transendothelial migration as a specific mechanism in animals receiving adjuvant only.

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CircNFIC Balances Inflammation and Apoptosis by Sponging miR-30e-3p and Regulating DENND1B Expression

Cited by 12 publications

References 68 publications

Dysregulation of miRNA-30e-3p targeting IL-1β in an international cohort of systemic autoinflammatory disease patients

Dysregulation of miRNA-30e-3p targeting IL-1β in an international cohort of systemic autoinflammatory disease patients

CircPLXNA2 Affects the Proliferation and Apoptosis of Myoblast through circPLXNA2/gga-miR-12207-5P/MDM4 Axis

Identification and characterization of miRNAs in spleens of sheep subjected to repetitive vaccination

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