CircRNA circFADS2 is under-expressed in sepsis and protects lung cells from LPS-induced apoptosis by downregulating miR-133a

Niu, Fang; Liang, Xiaofeng; Ni, Jindi; Xia, Zhuye; Jiang, Lijing; Wang, Hong; Liu, Hongjie; Shen, Guofeng; Li, Xiang

doi:10.1186/s12950-022-00300-3

Cited by 10 publications

(6 citation statements)

References 35 publications

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“…At present, increasingly, reports have confirmed that circRNAs could act as ceRNAs to sponge miRNAs and ultimately regulate the expression of target genes (23). Meanwhile, circRNAs have been manifested to mediate SA-ALI progression by binding miRNAs (24). The abundance of miR-940 was identified to be declined in sepsis patients and cecal ligation-perforation-stimulated sepsis animal models, and overexpression of miR-940 alleviated injury and inflammatory processes in sepsis models (25).…”

Section: Discussionmentioning

confidence: 99%

Interfering Hsa_circ_0001226 Mitigates LPS-Induced Beas-2b Cell Injury by Regulating Mir-940/Tgfbr2 Pathway

Mo,

Yi,

Bei

et al. 2023

Shock

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Background: Sepsis-associated acute lung injury (SA-ALI) is a serious threat to human health. A growing body of evidence suggested that circular RNAs may be involved in ALI progression. The aim of this study was to investigate the effect and mechanism of circ_0001226 on lipopolysaccharide (LPS)–induced BEAS-2B cells. Methods: BEAS-2B cells were stimulated with LPS to establish a SA-ALI cell model. The expression of circ_0001226, miR-940, and transforming growth factor beta receptor II (TGFBR2) were monitored by quantitative real-time polymerase chain reaction. Cell proliferation and apoptosis were evaluated by the Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine assay, and flow cytometry. The levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α were calculated by enzyme-linked immunosorbent assay. Western blot was implemented to test the protein levels of PCNA, Bax, and TGFBR2. Dual-luciferase reporter assay and RNA pull-down assay were adopted to investigate the interaction between circ_0001226 and miR-940, as well as TGFBR2 and miR-940. Results: The levels of circ_0001226 and TGFBR2 were elevated, and miR-940 was decreased in SA-ALI serum specimens and LPS-evoked BEAS-2B cells. Besides that, circ_0001226 interference contributed to cell proliferation and restrained apoptosis and inflammation in LPS-induced BEAS-2B cells. Mechanically, circ_0001226 worked as a molecular sponge of miR-940 to regulate TGFBR2 expression. Conclusion: Circ_0001226 deficiency weakened LPS-mediated proliferation inhibition and inflammatory processes in BEAS-2B cells by binding miR-940 and regulating TGFBR2.

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Section: Discussionmentioning

confidence: 99%

Interfering Hsa_circ_0001226 Mitigates LPS-Induced Beas-2b Cell Injury by Regulating Mir-940/Tgfbr2 Pathway

Mo,

Yi,

Bei

et al. 2023

Shock

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“…In our study, the increased production of miR-133a in the inflammatory adipose tissues, ovaries of obese and LPS-treated mice, and LPS-treated granulosa cells indicated that increased expression of miR-133a is associated with inflammatory status. Accordingly, in two recent clinical studies, high miR-133a levels were found in the serum of sepsis patients and LPS-treated human bronchial epithelial cells [ 45 , 46 ] . Therefore, HFD induced the hypertrophy of adipose cells and the proinflammatory polarization state of macrophages, which led to the release of several inflammatory cytokines and other factors.…”

Section: Discussionmentioning

confidence: 99%

Obesity-induced inflammatory miR-133a mediates apoptosis of granulosa cells and causes abnormal folliculogenesis

Chen¹,

Wu²,

Han³

et al. 2023

ABBS

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Obesity has been reported to promote disordered folliculogenesis, but the exact molecular mechanisms are still not fully understood. In this study, we find that miR-133a is involved in obesity-induced follicular development disorder. After feeding with a high-fat diet (HFD) and fructose water for nine weeks, the mouse body weight is significantly increased, accompanied by an inflammatory state and increased expression of miR-133a in the adipose tissues and ovaries as well as accelerated follicle depletion. Although miR-133a is increased in the fat and ovaries of HFD mice, the increased miR-133a in the HFD ovaries is not derived from exosome transferred from obese adipose tissues but is synthesized by ovarian follicular cells in response to HFD-induced inflammation. In vivo experiments show that intrabursal injection of miR-133a agomir induces a decrease in primordial follicles and an increase in antral follicles and atretic follicles, which is similar to HFD-induced abnormal folliculogenesis. Overexpression of miR-133a modestly promotes granulosa cell apoptosis by balancing the expression of anti-apoptotic proteins such as C1QL1 and XIAP and pro-apoptotic proteins such as PTEN. Overall, this study reveals the function of miR-133a in obesity-induced ovarian folliculogenesis dysfunction and sheds light on the etiology of female reproductive disorders.

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“…Genomics of sepsis hint that patients present inflammation and immunosuppression with altered expression levels of most genes 5 . In addition, some molecular players have been identified to be potential targets for the treatment of organ failure in patients with sepsis, such as microRNAs (miRNAs) and circular RNAs (circRNAs) 6 . These transcripts have also been illustrated to be related to the pathogenesis of multiple organ system failures 7 .…”

Section: Introductionmentioning

confidence: 99%

“…In addition, circRNAs can regulate a variety of molecular mechanisms, including inflammation and immune responses, as well as a variety of biological processes in various metabolic organs 11 . For example, altering circ-fatty acid desaturase 2 or circ_0001679 at the gene level can inhibit sepsis-induced ALI progression 6,12 . CircRNA protein tyrosine kinase 2 (circPTK2) has attracted academic attention in the aspect of malignancy [13][14][15] and has also been studied to mediate Circular RNA protein tyrosine kinase 2 aggravates pyroptosis and inflammation in septic lung tissue by promoting microRNA-766/ eukaryotic initiation factor 5A axis-mediated ATP efflux apoptosis and inflammatory response in sepsis-induced myocardial injury 16 .…”

Section: Introductionmentioning

confidence: 99%

Circular RNA protein tyrosine kinase 2 aggravates pyroptosis and inflammation in septic lung tissue by promoting microRNA-766/eukaryotic initiation factor 5A axis-mediated ATP efflux

Ding

Zhu

2023

Acta Cir. Bras.

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Purpose: Sepsis is characterized by an acute inflammatory response to infection, often with multiple organ failures, especially severe lung injury. This study was implemented to probe circular RNA (circRNA) protein tyrosine kinase 2 (circPTK2)-associated regulatory mechanisms in septic acute lung injury (ALI). Methods: A cecal ligation and puncture-based mouse model and an lipopolysaccharides (LPS)-based alveolar type II cell (RLE-6TN) model were generated to mimic sepsis. In the two models, inflammation-and pyroptosisrelated genes were measured. Results: The degree of lung injury in mice was analyzed by hematoxylin and eosin (H&E) staining and the apoptosis was by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining. In addition, pyroptosis and toxicity were detected in cells. Finally, the binding relationship between circPTK2, miR-766, and eukaryotic initiation factor 5A (eIF5A) was detected. Data indicated that circPTK2 and eIF5A were up-regulated and miR-766 was down-regulated in LPS-treated RLE-6TN cells and lung tissue of septic mice. Lung injury in septic mice was ameliorated after inhibition of circPTK2. Conclusion:It was confirmed in the cell model that knockdown of circPTK2 effectively ameliorated LPS-induced ATP efflux, pyroptosis, and inflammation. Mechanistically, circPTK2 mediated eIF5A expression by competitively adsorbing miR-766. Taken together, circPTK2/ miR-766/eIF5A axis ameliorates septic ALI, developing a novel therapeutic target for the disease.

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CircRNA circFADS2 is under-expressed in sepsis and protects lung cells from LPS-induced apoptosis by downregulating miR-133a

Cited by 10 publications

References 35 publications

Interfering Hsa_circ_0001226 Mitigates LPS-Induced Beas-2b Cell Injury by Regulating Mir-940/Tgfbr2 Pathway

Interfering Hsa_circ_0001226 Mitigates LPS-Induced Beas-2b Cell Injury by Regulating Mir-940/Tgfbr2 Pathway

Obesity-induced inflammatory miR-133a mediates apoptosis of granulosa cells and causes abnormal folliculogenesis

Circular RNA protein tyrosine kinase 2 aggravates pyroptosis and inflammation in septic lung tissue by promoting microRNA-766/eukaryotic initiation factor 5A axis-mediated ATP efflux

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