CCAT1 lncRNA Promotes Inflammatory Bowel Disease Malignancy by Destroying Intestinal Barrier via Downregulating miR-185-3p

Ma, Dan; Cao, Yingying; Wang, Zhenhua; He, Jie; Chen, Huimin; Xiong, Hua; Ren, Linlin; Shen, Chaoqin; Zhang, Xinyu; Yan, Yuqing; Yan, Tingting; Guo, Fangfang; Xuan, Baoqin; Cui, Zhe; Ye, Guangyao; Fang, Jing‐Yuan; Chen, Haoyan; Hong, Jie

doi:10.1093/ibd/izy381

Cited by 60 publications

(55 citation statements)

References 39 publications

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“…For instance, exosomal miR‐342‐5p was confirmed to protect the heart against the myocardial ischemia/reperfusion injury 22 . CCAT1/miR‐185‐3p/MLCK signaling pathway promotes the inflammatory bowel disease malignancy by destroying the intestinal barrier 23 . Besides, miR‐103 enhanced LPS‐caused inflammation damage by silencing c‐Myc in HK‐2 cells 24 .…”

Section: Discussionmentioning

confidence: 99%

Plasma exosomal miRNAs involved in endothelial injury in microscopic polyangiitis patients

et al. 2020

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Microscopic polyangiitis (MPA) is a systemic autoimmune disease that primarily affects the small and medium blood vessels. Endothelial injury is one of the pathological hallmarks of MPA. However, the pathogenesis for this has not yet been fully elucidated. Exosomal microRNAs (miRNAs) have recently emerged as a new molecular pattern involved in the endothelial injury in other diseases. Hence, we speculated that MPA plasma-derived exosomes (MPA-exo) could induce the endothelial injury, which was likely to be aroused by the dysregulated exosomal miRNAs in MPA. In the present study, plasma-derived exosomes were isolated and identified. MPA-exo could be internalized by human renal glomerular endothelial cells (HRGECs) in vitro and induced HRGECs injury. Subsequently, a series of differentially expressed miRNAs in MPAexo were identified by high-throughput sequencing analysis. Further bioinformatics analysis for the target genes of these differentially expressed miRNAs showed a potential mechanism for their possible role in MPA endothelial injury. Notably, we revealed a considerable correlation between miR-185-3p, miR-125a-3p, and clinical parameters. In conclusion, the current study revealed that differentially expressed miRNAs in MPA-exo are associated with the endothelial injury. Our results suggested that these miRNAs and their target genes might be involved in the inflammation process of MPA. K E Y W O R D Shigh-throughput sequencing, microRNA profile, plasma exosomes 6216 | WANG et Al.

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Section: Discussionmentioning

confidence: 99%

Plasma exosomal miRNAs involved in endothelial injury in microscopic polyangiitis patients

et al. 2020

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“…These two ncRNAs supported the regular effect of the intestinal barrier by mediating the production of TJ proteins ZO-1 and occludin, as well as MAZ 90 . Another lncRNA, colon cancer-associated transcript-1 (CCAT1), over-expressed in IBD tissues compared with in normal tissues and may be associated with the development of IBD 91 . CCAT1 can serve as miRNA-185-3p sponge and maintain the stability of myosin light chain kinase (MLCK) mRNA by decreasing miRNA-185-3p binding to MLCK mRNA in Caco-2 cells 91 .…”

Section: Other Lncrnasmentioning

confidence: 99%

“…Another lncRNA, colon cancer-associated transcript-1 (CCAT1), over-expressed in IBD tissues compared with in normal tissues and may be associated with the development of IBD 91 . CCAT1 can serve as miRNA-185-3p sponge and maintain the stability of myosin light chain kinase (MLCK) mRNA by decreasing miRNA-185-3p binding to MLCK mRNA in Caco-2 cells 91 . MLCK and its phosphorylation product regulated TJs assembly and increased intestinal permeability 91 .…”

Section: Other Lncrnasmentioning

confidence: 99%

Which long noncoding RNAs and circular RNAs contribute to inflammatory bowel disease?

et al. 2020

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Inflammatory bowel disease (IBD), a chronic relapsing gastrointestinal inflammatory disease, mainly comprises ulcerative colitis (UC) and Crohn's disease (CD). Although the mechanisms and pathways of IBD have been widely examined in recent decades, its exact pathogenesis remains unclear. Studies have focused on the discovery of new therapeutic targets and application of precision medicine. Recently, a strong connection between IBD and noncoding RNAs (ncRNAs) has been reported. ncRNAs include microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). The contributions of lncRNAs and circRNAs in IBD are less well-studied compared with those of miRNAs. However, lncRNAs and circRNAs are likely to drive personalized therapy for IBD. They will enable accurate diagnosis, prognosis, and prediction of therapeutic responses and promote IBD therapy. Herein, we briefly describe the molecular functions of lncRNAs and circRNAs and provide an overview of the current knowledge of the altered expression profiles of lncRNAs and circRNAs in patients with IBD. Further, we discuss how these RNAs are involved in the nosogenesis of IBD and are emerging as biomarkers. Facts • long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) are involved in the pathogenesis of inflammatory bowel disease (IBD). • Moreover, certain lncRNAs and circRNAs are potential biomarkers of IBD. • The contributions of lncRNAs and circRNAs in IBD will become hot spots in future studies. Open questions • lncRNAs and circRNAs show altered expression profile in patients with IBD compared with those in healthy controls. • Which and how are lncRNAs and circRNAs involved in the internal mechanism of IBD? • Will lncRNAs and circRNAs serve as clinical biomarkers of IBD?

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“…Liu et al [23] analyzed microRNAs in alcoholic liver diseases using microarrays and found that miR-185 can participate in immune response, inflammatory response and glutathione metabolism. Ma et al [24] found that the…”

Section: Introductionmentioning

confidence: 99%

ssc-miR-185 targets cell division cycle 42 and promotes the proliferation of intestinal porcine epithelial cell

Wang

Xie

et al. 2021

Anim Biosci

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Objective: microRNAs (miRNAs) can play a role in a variety of physiological and pathological regulation, and its role is achieved by regulating the expression of target genes. Our previous high-throughput sequencing found that ssc-miR-185 plays an important regulatory role in piglet diarrhea, but its specific target genes and functions in intestinal porcine epithelial cell (IPEC-J2) are still unclear. We intended to verify the target relationship between porcine miR-185 and cell division cycle 42 (CDC42) gene in IPEC-J2, and explored the effect of miR-185 on the proliferation of IPEC-J2 cells. Methods: The TargetScan, miRDB and miRanda softwares were used to predict the target genes of porcine miR-185, and CDC42 was selected as a candidate target gene. The CDC42-3'UTR-wild type (WT) and CDC42-3'UTR-mutant type (MUT) segments were successfully cloned into pmirGLO luciferase vector, and the luciferase activity was detected after co-transfection with miR-185 mimics and CDC42-3'UTR. The expression level of CDC42 was analyzed using qPCR and Western blot. The proliferation of IPEC-J2 was detected using CCK-8, MTT and EdU assays. Results: Double enzyme digestion and sequencing confirmed that CDC42-3'UTR-WT and CDC42-3'UTR-MUT were successfully cloned into pmirGLO luciferase reporter vector, and the luciferase activity was significantly reduced after co-transfection with miR-185 mimics and CDC42-3'UTR (WT). Further we found that the mRNA and protein expression level of CDC42 were down-regulated after transfection with miR-185 mimics, while the opposite trend was observed after transfection with miR-185 inhibitor (p < 0.01). In addition, the CCK-8, MTT and EdU results demonstrated that miR-185 promotes IPEC-J2 cells proliferation by targeting CDC42. Conclusion: These findings indicate that porcine miR-185 can directly target CDC42 and promote the proliferation of IPEC-J2 cells. However, the detailed regulatory mechanism of miR-185/CDC42 axis in piglets resistance to diarrhea is yet to be further investigation.

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CCAT1 lncRNA Promotes Inflammatory Bowel Disease Malignancy by Destroying Intestinal Barrier via Downregulating miR-185-3p

Cited by 60 publications

References 39 publications

Plasma exosomal miRNAs involved in endothelial injury in microscopic polyangiitis patients

Plasma exosomal miRNAs involved in endothelial injury in microscopic polyangiitis patients

Which long noncoding RNAs and circular RNAs contribute to inflammatory bowel disease?

ssc-miR-185 targets cell division cycle 42 and promotes the proliferation of intestinal porcine epithelial cell

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