nach oben

Erschienen in:

29.04.2019 | Original Article—Alimentary Tract

Integrated analysis of circRNAs and mRNAs expression profile revealed the involvement of hsa_circ_0007919 in the pathogenesis of ulcerative colitis

verfasst von: Tingting Wang, Ning Chen, Weixia Ren, Fangfang Liu, Fangfang Gao, Lei Ye, Ying Han, Yujun Zhang, Yulan Liu

Erschienen in: Journal of Gastroenterology | Ausgabe 9/2019

Einloggen, um Zugang zu erhalten

Abstract

Background

Ulcerative colitis (UC) is characterized by chronic inflammation in the colon and epigenetic factors underlying the occurrence. Circular RNAs (circRNAs) have been under intensive focus due to the circular construct and gene-regulating functions. However, the changes and roles of circRNAs in UC remain unknown.

Methods

Microarrays were used to detect the differentially expressed genes, and quantitative real-time PCR was used to identify the changes in UC. In silico analyses were performed to predict the functions of circRNAs and mRNAs. In vitro, epithelial cell lines were stimulated by pro-inflammation effectors to test the alterations in circRNAs. CircRNAs–microRNAs–mRNAs network clarified the potential mechanisms underlying circRNAs in UC. The binding site between hsa_circ_0007919 and miR-138 or let-7a was verified using dual-luciferase assay.

Results

A total of 264 significantly dysregulated circRNAs and 1869 differentially expressed mRNAs in inflamed mucosa were compared with the non-inflamed mucosa in UC. Hsa_circ_0004662 and hsa_circ_0007919 were altered largely in UC tissues. Hsa_circ_0007919 was reduced persistently after inflammatory treatments, and it was relevant to Mayo endoscopic subscores and the expression of tight junction molecules. Finally, hsa_circ_0007919 could harbor miR-138, and let-7a to regulate the targeted mRNAs EPC1 and VIPR1.

Conclusions

Several circRNAs were differentially expressed in UC. Hsa_circ_0007919 is related to clinical characteristics and epithelial integrity by binding to hsa-let-7a, hsa-miR-138 to regulate the target genes. CircRNAs, especially hsa_circ_0007919, are associated with the pathogenesis and development of UC, with potential diagnostic and therapeutic implications.

Nur mit Berechtigung zugänglich

Magro F, Gionchetti P, Eliakim R, et al. Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohn's Colitis. 2017;11:649–70.CrossRef

Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017;390:2769–78.CrossRefPubMed

Costello CM, Mah N, Hasler R, et al. Dissection of the inflammatory bowel disease transcriptome using genome-wide cDNA microarrays. PLoS Med. 2005;2:e199.CrossRefPubMedPubMedCentral

Ventham NT, Kennedy NA, Nimmo ER, et al. Beyond gene discovery in inflammatory bowel disease: the emerging role of epigenetics. Gastroenterology. 2013;145:293–308.CrossRefPubMed

Mirza AH, Berthelsen CH, Seemann SE, et al. Transcriptomic landscape of lncRNAs in inflammatory bowel disease. Genome Med. 2015;7:39.CrossRefPubMedPubMedCentral

He C, Yu T, Shi Y, et al. MicroRNA 301A promotes intestinal inflammation and colitis-associated cancer development by inhibiting BTG1. Gastroenterology. 2017;152:1434–48.e15.CrossRefPubMed

Min M, Peng L, Yang Y, et al. MicroRNA-155 is involved in the pathogenesis of ulcerative colitis by targeting FOXO3a. Inflamm Bowel Dis. 2014;20:652–9.CrossRefPubMed

Hsu MTC-PM. Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells. Nature. 1979;280:339–40.CrossRefPubMed

Jeck WR, Sorrentino JA, Wang K, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 2013;19:141–57.CrossRefPubMedPubMedCentral

10.

Salzman JCR, Olsen MN, Wang PL, et al. Cell-type specifc features of circular RNA expression. PLoS Genet. 2013;9(9):e1003777.CrossRefPubMedPubMedCentral

11.

Militello G, Weirick T, John D, et al. Screening and validation of lncRNAs and circRNAs as miRNA sponges. Br Bioinform. 2017;18:780–8.

12.

Piwecka M, Glazar P, Hernandez-Miranda LR, et al. Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function. Science. 2017;357(6357):eaam8526. https://doi.org/10.1126/science.aam8526.CrossRefPubMed

13.

Li Z, Huang C, Bao C, et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol. 2015;22:256–64.CrossRefPubMed

14.

Ashwal-Fluss R, Meyer M, Pamudurti NR, et al. circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 2014;56:55–66.CrossRefPubMed

15.

Han D, Li J, Wang H, et al. Circular RNA circMTO1 acts as the sponge of microRNA-9 to suppress hepatocellular carcinoma progression. Hepatology. 2017;66:1151–64.CrossRefPubMed

16.

Liu Q, Zhang X, Hu X, et al. Circular RNA related to the chondrocyte ECM regulates MMP13 expression by functioning as a MiR-136 'Sponge' in human cartilage degradation. Sci Rep. 2016;6:22572.CrossRefPubMedPubMedCentral

17.

Iparraguirre L, Munoz-Culla M, Prada-Luengo I, et al. Circular RNA profiling reveals that circular RNAs from ANXA2 can be used as new biomarkers for multiple sclerosis. Hum Mol Genet. 2017;26:3564–72.CrossRefPubMed

18.

Yuan G, Chen T, Zhang H, et al. Comprehensive analysis of differential circular RNA expression in a mouse model of colitis-induced colon carcinoma. Mol Carcinog. 2018;57:1825–34.CrossRefPubMed

19.

Zeng K, Chen X, Xu M, et al. CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7. Cell Death Dis. 2018;9(4):417.CrossRefPubMedPubMedCentral

20.

Wang H, Chao K, Ng SC, et al. Pro-inflammatory miR-223 mediates the cross-talk between the IL23 pathway and the intestinal barrier in inflammatory bowel disease. Genome Biol. 2016;17:58.CrossRefPubMedPubMedCentral

21.

Qiao Y, Cai C, Shen J, et al. Circular RNA expression alterations in colon tissues of Crohn's disease patients. Mol Med Rep. 2019;19:4500–6.PubMed

22.

Paramsothy S, Kamm MA, Kaakoush NO, et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet. 2017;389:1218–28.CrossRefPubMed

23.

Matsuhisa K, Watari A, Iwamoto K, et al. Lignosulfonic acid attenuates NF-kappaB activation and intestinal epithelial barrier dysfunction induced by TNF-alpha/IFN-gamma in Caco-2 cells. J Nat Med. 2018;72:448–55.CrossRefPubMed

24.

Stauffer JS, Manzano LA, Balch GC, et al. Development and characterization of normal colonic epithelial cell lines derived from normal mucosa of patients with colon cancer. Am J Surg. 1995;169:190–6.CrossRefPubMed

25.

Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2008;4:44.CrossRef

26.

Ravasz E, Somera AL, Mongru DA, et al. Hierarchical organization of modularity in metabolic networks. Science. 2002;297:1551.CrossRefPubMed

27.

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 2001;25:402–8.CrossRefPubMed

28.

Pasquinelli AE. MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet. 2012;13:271.CrossRefPubMed

29.

Enright AJ, John B, Gaul U, et al. MicroRNA targets in Drosophila. Genome Biol. 2004;5:R1.CrossRef

30.

Barrett SP, Wang PL, Salzman J. Circular RNA biogenesis can proceed through an exon-containing lariat precursor. eLife. 2015;4:e07540.CrossRefPubMedPubMedCentral

31.

Wu F, Huang Y, Dong F, et al. Ulcerative colitis-associated long noncoding RNA, BC012900, regulates intestinal epithelial cell apoptosis. Inflamm Bowel Dis. 2016;22:782–95.CrossRefPubMed

32.

Sitkovsky M, Lukashev D. Regulation of immune cells by local-tissue oxygen tension: HIF1 alpha and adenosine receptors. Nat Rev Immunol. 2005;5:712–21.CrossRefPubMed

33.

Ishihara S, Nishikimi A, Umemoto E, et al. Dual functions of Rap1 are crucial for T-cell homeostasis and prevention of spontaneous colitis. Nat Commun. 2015;6:8982.CrossRefPubMed

34.

Mateescu RB, Bastian AE, Nichita L, Marinescu M, et al. Vascular endothelial growth factor—key mediator of angiogenesis and promising therapeutical target in ulcerative colitis. Rom J Morphol Embryol. 2017;58:1339–455.PubMed

35.

Dieckgraefe BK, Crimmins DL, Landt V, et al. Expression of the regenerating gene family in inflammatory Bowel disease mucosa: reg Iα upregulation, processing, and antiapoptotic activity. J Investig Med. 2002;50:421–34.CrossRefPubMed

36.

LalNag M, Morin PJ. The claudins. Genome Biol. 2009;10:235.CrossRef

37.

Amasheh S, Meiri N, Gitter AH, et al. Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells. J Cell Sci. 2002;115:4969.CrossRefPubMed

38.

Amoozadeh Y, Dan Q, Xiao J, et al. Tumor necrosis factor-alpha induces a biphasic change in claudin-2 expression in tubular epithelial cells: role in barrier functions. Am J Physiol Cell Physiol. 2015;309:C38–C50.CrossRefPubMedPubMedCentral

39.

Poritz LS, Garver KI, Green C, et al. Loss of the tight junction protein ZO-1 in dextran sulfate sodium induced colitis. J Surg Res. 2007;140:12–9.CrossRefPubMed

40.

Clark PM, Dawany N, Dampier W, et al. Bioinformatics analysis reveals transcriptome and microRNA signatures and drug repositioning targets for IBD and other autoimmune diseases. Inflamm Bowel Dis. 2012;18:2315–33.CrossRefPubMed

41.

Shouval DS, Biswas A, Kang YH, et al. Interleukin 1β mediates intestinal inflammation in mice and patients with interleukin 10 receptor deficiency. Gastroenterology. 2016;151:1100–4.CrossRefPubMed

42.

Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013;495:333–8.CrossRefPubMed

43.

Zheng Q, Bao C, Guo W, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun. 2016;7:11215.CrossRefPubMedPubMedCentral

44.

Valmiki S, Ahuja V, Paul J. MicroRNA exhibit altered expression in the inflamed colonic mucosa of ulcerative colitis patients. World J Gastroenterol. 2017;23:5324–32.CrossRefPubMedPubMedCentral

45.

Jönsson M, Norrgård Ö, Forsgren S. Epithelial expression of vasoactive intestinal peptide in ulcerative colitis: down-regulation in markedly inflamed colon. Dig Dis Sci. 2012;57:303–10.CrossRefPubMed

46.

Csaba Z, Dournaud P. Cellular biology of somatostatin receptors. Neuropeptides. 2001;35:1–23.CrossRefPubMed

47.

Geng H, Bu HF, Liu F, et al. In inflamed intestinal tissues and epithelial cells, interleukin 22 signaling increases expression of H19 long noncoding RNA which promotes mucosal regeneration. Gastroenterology. 2018;155:144–55.CrossRefPubMed

Titel: Integrated analysis of circRNAs and mRNAs expression profile revealed the involvement of hsa_circ_0007919 in the pathogenesis of ulcerative colitis
verfasst von: Tingting Wang
Ning Chen
Weixia Ren
Fangfang Liu
Fangfang Gao
Lei Ye
Ying Han
Yujun Zhang
Yulan Liu
Publikationsdatum: 29.04.2019
Verlag: Springer Japan
Erschienen in: Journal of Gastroenterology / Ausgabe 9/2019
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI: https://doi.org/10.1007/s00535-019-01585-7

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

19.04.2024 | Vorhofflimmern | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Integrated analysis of circRNAs and mRNAs expression profile revealed the involvement of hsa_circ_0007919 in the pathogenesis of ulcerative colitis

Abstract

Background

Methods

Results

Conclusions

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Parodontalbehandlung verbessert Prognose bei Katheterablation

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Denken Sie bei starker Blutung auch an die Hemmkörper-Hämophilie

Update Innere Medizin

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Background

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 9/2019

The course of elderly patients with persistent hepatitis C virus infection without hepatocellular carcinoma

Time trends in the incidence of esophageal adenocarcinoma, gastric adenocarcinoma, and superficial esophagogastric junction adenocarcinoma

Epstein–Barr virus status is a promising biomarker for endoscopic resection in early gastric cancer: proposal of a novel therapeutic strategy

A simple and practical index predicting the prognoses of the patients with well-differentiated pancreatic neuroendocrine neoplasms

The mesenchymal stem cell secretome as an acellular regenerative therapy for liver disease

Polyethylene glycol 3350 plus electrolytes for chronic constipation: a 2-week, randomized, double-blind, placebo-controlled study with a 52-week open-label extension

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Parodontalbehandlung verbessert Prognose bei Katheterablation

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Denken Sie bei starker Blutung auch an die Hemmkörper-Hämophilie

Update Innere Medizin