ارزیابی بیان ژن (lncRNA ANRIL(CDKN2B-AS1 در مبتلایان بیماری‌های التهابی روده

نویسندگان
فریبا رشید 1
غلامرضا جوادی 1
حمید اسدزاده عقدایی 2
1 دانشگاه آزاد اسلامی واحد علوم و تحقیقات تهران
2 مرکز تحقیقات اپیدمیولوژی پایه و مولکولی اختلالات گوارشی، موسسه تحقیقات گوارش و بیماری های کبدی، دانشگاه علوم پزشکی شهید بهشتی، تهران
چکیده
مقدمه

بیماری‌های التهابی روده سبب التهاب مزمن و عودکننده‌ی دستگاه گوارش می‌شوند و به دو بیماری کرون و کولیت اولسراتیو تقسیم‌بندی می‌گردند. در این مطالعه به‌منظور دست‌یابی به بیومارکری برای تشخیص و پیش‌آگهی بیماری‌های التهابی روده، بیان ژن lncRNA ANRIL (CDKN2B-AS1) مورد بررسی قرار گرفت.

مواد و روش‌‌ها

این مطالعه شامل 33 بیمار مبتلا به بیماری‌های التهابی روده و 20 فرد سالم است که به پژوهشکده کبد و گوارش دانشگاه شهید بهشتی مراجعه کرده بودند. RNA از نمونه‌های بافتی استخراج‌شده و cDNA آن‌ها ساخته شد. تکثیر ژن‌ها با هدف اندازه‌گیری بیان ژن توسط واکنش Real time PCR کمی صورت گرفت و داده‌های خام با استفاده از نرم‌افزار Rest تجزیه‌وتحلیل شدند. داده‌های حاصل از مقایسه بافت‌های بیمار و سالم از طریق آنالیز Student’s t-test و One-way ANOVA مورد ارزیابی قرار گرفتند.

یافته‌‌ها

در این مطالعه‌ هردو بیماری کرون و کولیت بر اساس تمامی مشخصات بیماری که التهاب را نیز شامل می‌شد موردبررسی قرار گرفتند و اختلاف معناداری در میان بیماران کرون و کولیت در مقایسه با افراد کنترل مشاهده نگردید (1340/0=P). در بررسی میزان بیان lncRNA ANRIL در دو جنس زن و مرد نیز اختلاف معنی‌‌داری مشاهده نگردید (2571/0=P).

نتیجه‌‌گیری

نتایج حاصل از آنالیز داده‌ها نشان می‌دهد که نمی‌توان از lncRNA ANRIL به ‌عنوان بیومارکری جهت تشخیص و تمیز بیماری‌های التهابی روده در جامعه ایرانی استفاده کرد.
کلیدواژه‌ها
بیماری‌های التهابی روده
(lncRNA ANRIL(CDKN2B-AS1
بیماری کرون
کولیت اولسراتیو

عنوان مقاله English

Evaluation of lncRNA ANRIL (CDKN2B-AS1) gene expression in patients with inflammatory bowel disease

نویسندگان English

fariba rashid 1
Gholamreza Javadi 1
Hamid Asadzadeh Aghdaei 2
1 Islamic Azad University, Science and Research Branch, Tehran
2 Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
چکیده English

Introduction and Aims: Inflammatory bowel disease causes chronic and relapsing gastrointestinal inflammation that classified into Crohn's disease and ulcerative colitis. In this study, in order to obtain biomarker for diagnosis and prognosis of inflammatory bowel disease, lncRNA ANRIL (CDKN2B-AS1) gene expression was evaluated.

Materials and Methods: This study included 33 IBD patients and 20 healthy individuals who referred to the Research Institute for Gastroenterology & Liver Diseases ShahidBeheshti University.RNA extracted from tissue samples and subsequently, their cDNA was synthesized. Gene amplification was performed with the aim of measuring the gene expression by a real-time quantitative PCR (qRT-PCR) reaction. Data from comparing healthy and healthy tissues were assessed by Student's t-test and One-way ANOVA.

Results: In this study, both Crohn's disease and ulcerative colitis were evaluated based on Features of the disease that included inflammation, and no significant difference was found between Crohn's disease and ulcerative colitis patients compared to healthy individuals (P value=0.1340). Also, there was no significant difference in the expression of lncRNA ANRIL in both males and females (P value = 0.2571).

Conclusions: The results of the data analysis show that lncRNA ANRIL cannot be used as a biomarker for the diagnosis and differentiation of inflammatory bowel disease in Iranian society.

کلیدواژه‌ها English

Inflammatory bowel disease
LncRNA ANRIL (CDKN2BAS1)
Crohn's disease
Ulcerative colitis
1. Xavier R, Podolsky D. Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007;448(7152):427-34.
2. Cummins EP, Crean D. Hypoxia and inflammatory bowel disease. Microbes Infect 2017;19(3):210-21.
3. Van Limbergen J, Radford-Smith G, Satsangi J. Advances in IBD genetics. Nat Rev Gastroenterol Hepatol 2014;11(6):372-85.
4. Cleynen I, Boucher G, Jostins L, Schumm LP, Zeissig S, Ahmad T, et al. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study. Lancet 2016;387(10014):156-67.
5. Molodecky NA, Soon S, Rabi DM, Ghali WA, Ferris M, Chernoff G, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 2012;142(1):46-54. e42.
6. Fulforth JM, Gearry RB. Inflammatory bowel disease risk and the environment: Where to next? Journal of gastroenterology and hepatology 2016;31(6):1074-5.
7. Gearry RB. IBD and environment: are there differences between east and west. Dig Dis 2016;34(1-2):84-9.
8. Ponder A, Long MD. A clinical review of recent findings in the epidemiology of inflammatory bowel disease. Clin Epidemiol 2013;5:237-47.
9. Kellermayer R. Epigenetics and the developmental origins of inflammatory bowel diseases. Can J Gastroenterol 2012;26(12):909-15.
10. Costa FF. Non-coding RNAs, epigenetics and complexity. Gene 2008;410(1):9-17.
11. Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 2012;22(9):1775-89.
12. Chen G, Wang Z, Wang D, Qiu C, Liu M, Chen X, et al. LncRNADisease: a database for long-non-coding RNA-associated diseases. Nucleic Acids Res 2012;41:D983-6.
13. Edgington-Mitchell LE. Long noncoding RNAs: novel links to inflammatory bowel disease?. Am J Physiol Gastrointest Liver Physiol 2016;311(3):G444-5.
14. Noori-Daloii MR, Eshaghkhani Y. lncRNAs: significance and function mechanisms. MEDICAL SCIENCES 2015;25(2):79-94. [Persian]
15. Mirza AH, Berthelsen CH, Seemann SE, Pan X, Frederiksen KS, Vilien M, et al. Transcriptomic landscape of lncRNAs in inflammatory bowel disease. Genome Med 2015;7(1):39.
16. Chen D, Liu J, Zhao H-Y, Chen Y-P, Xiang Z, Jin X. Plasma long noncoding RNA expression profile identified by microarray in patients with Crohn’s disease. World J Gastroenterol 2016;22(19):4716-31.
17. Wu F, Huang Y, Dong F, Kwon JH . Ulcerative colitis-associated long noncoding RNA, BC012900, regulates intestinal epithelial cell apoptosis. Inflamm Bowel Dis 2016;22(4):782-95.
18. Deng W, Wang J, Zhang J, Cai J, Bai Z, Zhang Z. TET2 regulates LncRNA‐ANRIL expression and inhibits the growth of human gastric cancer cells. IUBMB life 2016;68(5):355-64.
19. Zhang D, Sun G, Zhang H, Tian J, Li Y. Long non-coding RNA ANRIL indicates a poor prognosis of cervical cancer and promotes carcinogenesis via PI3K/AKT pathways. Biomed Pharmacother 2017;85:511-6.
20. Nie F-q, Sun M, Yang J-s, Xie M, Xu T-p, Xia R, et al. Long noncoding RNA ANRIL promotes non–small cell lung cancer cell proliferation and inhibits apoptosis by silencing KLF2 and P21 expression. Mol Cancer Ther 2015;14(1):268-77.
21. Huang M-d, Chen W-m, Qi F-z, Xia R, Sun M, Xu T-p, et al. Long non-coding RNA ANRIL is upregulated in hepatocellular carcinoma and regulates cell apoptosis by epigenetic silencing of KLF2. J Hematol Oncol 2015;8:1-14.
22. Naemura M, Murasaki C, Inoue Y, Okamoto H, Kotake Y. Long noncoding RNA ANRIL regulates proliferation of non-small cell lung cancer and cervical cancer cells. Anticancer Res 2015;35(10):5377-82.
23. Zhu H, Li X, Song Y, Zhang P, Xiao Y, Xing Y. Long non-coding RNA ANRIL is up-regulated in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic pathway. Biochem Biophys Res Commun 2015;467(2):223-8.
24. Jenke AC, Zilbauer M. Epigenetics in inflammatory bowel disease. Curr Opin Gastroenterol 2012;28(6):577-84.
25. Norouzinia M, Chaleshi V, Alizadeh AHM, Zali MR. Biomarkers in inflammatory bowel diseases: insight into diagnosis, prognosis and treatment. Gastroenterol Hepatol Bed Bench 2017;10(3):155.
26. Congrains A, Kamide K, Ohishi M, Rakugi H. ANRIL: molecular mechanisms and implications in human health. Int J Mol Sci 2013;14(1):1278-92.
27. Pothoulakis C, Iliopoulos D, Rankin R, Padua D. P-307 The Long Non-coding RNA, CDKN2B-AS1, Is Associated with IBD and Is Downregulated by TGF-beta. Inflammatory Bowel Diseases 2017;23:S98.
28. Khrom M, Potdar AA, Mengesha E, Li D, Targan SR, McGovern D, et al. 592 Gender-Stratified Analyses Identifies Sex-Specific IBD Associations. Gastroenterology 2018;154(6):S-125-S-6.
29. Vemuri R, Sylvia KE, Klein SL, Forster SC, Plebanski M, Eri R, et al. The microgenderome revealed: sex differences in bidirectional interactions between the microbiota, hormones, immunity and disease susceptibility. Semin Immunopathol 2018.
30. Alikhah A, Kakhki MP, Ahmadi A, Dehghanzad R, Boroumand MA, Behmanesh M. The role of lnc-DC long non-coding RNA and SOCS1 in the regulation of STAT3 in coronary artery disease and type 2 diabetes mellitus. J Diabetes Complications 2018;32(3):258-65.
31. Insenser M, Murri M, del Campo R, Martínez-García MÁ, Fernández-Durán E, Escobar-Morreale HF. Gut Microbiota and the Polycystic Ovary Syndrome: Influence of Sex, Sex Hormones, and Obesity. J Clin Endocrinol Metab 2018;103(7):2552-62.
32. Sarkar D, Leung EY, Baguley BC, Finlay GJ, Askarian-Amiri ME. Epigenetic regulation in human melanoma: past and future. Epigenetics 2015;10(2):103-21.