published Oct. 4<\/a> in the Journal of Clinical Investigation (JCI) Insight<\/i>, has found that a set of biomolecules known as microRNAs, specifically microRNA-31 (miR-31), can help predict which patients with Crohn\u2019s disease are at higher risk for the development of severe problems that may require surgical removal of the large intestine.<\/p>\n\u201cFor such a clinically heterogenous disease, this kind of molecular phenotyping is a major step towards personalization of medical therapy, said co-senior author Shehzad Z. Sheikh, MD, PhD, associate professor of medicine and genetics. \u201cThese results add to a series of papers from our group where we combine genomic technologies with rigorous validation in patient-derived, disease-relevant cell systems to develop molecular markers with prognostic utility.\u201d<\/p>\n
A key validation step in this research involved the generation of organoids or \u2018mini-guts\u2019 that architecturally and physiologically resemble the human intestine. Sheikh and colleagues derived organoids from Crohn\u2019s patients to preserve the molecular defects observed in the patient tissue.<\/p>\n
\u201cThis innovative system can serve as a personalized testing platform to screen therapeutic agents before administering them to the patient,\u201d Sheikh said.<\/p>\n
In the study, small RNA-sequencing was performed on adult colon tissue from 18 adults with Crohn\u2019s disease and 12 controls. Small RNA-sequencing was also performed on colon tissue from 76 children who were newly diagnosed with Crohn\u2019s but had not received any treatment yet, and 51 controls. In addition to these whole tissue assays, colonic epithelial cells and immune cells were isolated from colonic tissues and miR-31 expression was measured.<\/p>\n
These analyses found that in adults, low colonic miR-31 expression at the time of surgery was associated with worse disease outcomes, requiring an end ileostomy and later recurrence of disease. In children, low colonic miR-31 expression at the time of diagnosis was found to be associated with future development of strictures that required surgery.<\/p>\n
\u201cIn recent years there has been great success in deriving molecular signatures that classify several cancers into subtypes, including studies performed here at UNC,\u201d said co-senior author Terry Furey, PhD, associate professor of genetics and biology and a member of the UNC Lineberger Comprehensive Cancer Center. \u201cThese subtypes, then, have been shown to be useful in determining cancer progression and response to specific therapies. Our long-term goal, extending the work in this study, is to uncover molecular subtypes of Crohn\u2019s disease to not only increase our understanding of the root causes of the disease and the vast clinical heterogeneity, but also to more strategically use current therapies and provide the basis for new therapies that specifically target these subtypes.\u201d<\/p>\n
The third co-corresponding author is Praveen Sethupathy, PhD, associate professor of biomedical sciences at Cornell University, who established a collaboration with Drs. Sheikh and Furey while he was a faculty member at UNC from 2011-2017. \u201cWhile microRNAs as prognostic indicators of disease development has emerged as an exciting concept, there have been very few clinically actionable examples to date. We are excited about our findings because, while it is just the beginning and more work remains to be done, it opens the possibility of using microRNAs to improve clinical trial designs for Crohn\u2019s disease and developing more personalized therapeutic strategies for patients. Also, our study emphasizes the importance of epithelial biology in Crohn\u2019s disease, which merits deeper investigation to delineate mechanisms that underlie the etiology of different disease subtypes,\u201d Sethupathy said.<\/p>\n
Benjamin P. Keith, a graduate student in the Sheikh Lab, is first author of the study. He highlighted the importance of the methods the researchers used in the clinic to preserve patient tissue samples.<\/p>\n
\u201cPreserving tissue in this way usually results in heavily degraded mRNA,\u201d Keith said. \u201cBut our ability to accurately detect microRNA expression that was not degraded in fixed samples opens up future studies to a wealth of patient samples from across the country to further validate microRNA-31 and a suite of other microRNAs as prognostic markers of Crohn\u2019s disease,\u201d Keith said.<\/p>\n
UNC co-authors are Jasmine B. Barrow, Takahiko Toyonaga, PhD; Michelle Hoffner O\u2019Connor, Neil D. Shah, MD; Matthew S. Schaner, Elizabeth A. Wolber, Omar K. Trad, Greg R. Gipson, Shruti J. Saxena, Nicole Chaumont, MD; Timothy S. Sadiq, MD; Mark J. Koruda, MD; Paul A. Cotney, Nancy Albritton, MD, PhD; Dimitri G. Trembath, MD, PhD; and Francisco Sylvester, MD.<\/i><\/p>\n
This study was supported by funding from the Crohn\u2019s & Colitis Foundation, the National Institute of Environmental Health Sciences (NIEHS), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the American Diabetes Association (ADA), the UNC Nutrition Obesity Research Center, the UNC Center for Gastrointestinal Biology and Disease (CGIBD), the National Institute of General Medical Sciences (NIGMS), the Helmsley Charitable Trust, the National Cancer Institute (NCI) and the UNC University Cancer Research Fund.<\/i><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"
<\/p>\n
These findings by UNC School of Medicine researchers are an important step forward in designing more effective clinical trials and developing personalized Crohn\u2019s disease therapies.<\/p>\n","protected":false},"author":69419,"featured_media":4652,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"layout":"","cellInformation":"","apiCallInformation":"","footnotes":"","_links_to":"","_links_to_target":""},"categories":[97,2],"tags":[22],"class_list":["post-4651","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-gastroenterology","category-news","tag-22","odd"],"acf":[],"yoast_head":"\n
Genomic Study Finds New Role for MicroRNAs As Predictors of Crohn\u2019s Disease Progression | Department of Medicine<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.med.unc.edu\/medicine\/news\/genomic-study-finds-new-role-for-micrornas-as-predictors-of-crohn2019s-disease-progression\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Genomic Study Finds New Role for MicroRNAs As Predictors of Crohn\u2019s Disease Progression | Department of Medicine\" \/>\n<meta property=\"og:description\" content=\"These findings by UNC School of Medicine researchers are an important step forward in designing more effective clinical trials and developing personalized Crohn\u2019s disease therapies.\" \/>\n<meta property=\"og:url\" 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