Breaking News
January 19, 2019 - FDA Approves Ontruzant (trastuzumab-dttb), a Biosimilar to Herceptin
January 19, 2019 - Tobacco use linked with higher use of opioids and sedatives
January 19, 2019 - Study delves deeper into developmental dyslexia
January 19, 2019 - Anti-vaccination movement one of the top health threats in 2019 says WHO
January 19, 2019 - Newly developed risk score more effective at identifying type 1 diabetes
January 19, 2019 - Highly effective protocol to prepare cannabis samples for THC/CBD analysis
January 19, 2019 - Prinston Pharmaceutical Inc. Issues Voluntary Nationwide Recall of Irbesartan and Irbesartan HCTZ Tablets Due to Detection of a Trace Amount of Unexpected Impurity, N-Nitrosodiethylamine (NDEA) in the Products
January 19, 2019 - How does solid stress from brain tumors cause neuronal loss, neurologic dysfunction?
January 19, 2019 - $14.7 million partnership to supercharge vaccine development
January 19, 2019 - Ian Fotheringham receives Charles Tennant Memorial Lecture award
January 19, 2019 - Brain vital signs detect neurophysiological impairments in players with concussions
January 19, 2019 - Lack of job and poor housing conditions increased likelihood of people attending A&E
January 19, 2019 - Novel targeted drug delivery system improves conventional cancer treatments
January 19, 2019 - Rutgers study finds gene responsible for spread of prostate cancer
January 19, 2019 - Complications Higher Than Expected for Invasive Lung Tests
January 19, 2019 - 3-D printed implant promotes nerve cell growth to treat spinal cord injury
January 19, 2019 - Automated texts lead to improved outcomes after total knee or hip replacement surgery
January 19, 2019 - Poor cardiorespiratory fitness could increase risk of future heart attack, finds new study
January 19, 2019 - Drinking soft drinks while exercising in hot weather may increase risk of kidney disease
January 19, 2019 - Formlabs 3D prints anatomical models
January 19, 2019 - Heart-Healthy Living Also Wards Off Type 2 Diabetes
January 19, 2019 - Teaching Kids to Be Smart About Social Media (for Parents)
January 19, 2019 - Metabolite produced by gut microbiota from pomegranates reduces inflammatory bowel disease
January 19, 2019 - Researchers examine how spray from showers and toilets expose us to disease causing bacteria
January 19, 2019 - Behavioral experiments confirm that additional neurons improve brain function
January 19, 2019 - New study compares performance of real-time infectious disease forecasting models
January 19, 2019 - Obesity can be risk factor for developing renal cell carcinoma, confirms study
January 19, 2019 - New regulation designs on cigarette packs direct smokers’ attention to health warnings
January 19, 2019 - QIAGEN receives first companion diagnostic approval in Japan
January 19, 2019 - Study explores role of Dunning-Kruger effect in anti-vaccine attitudes
January 19, 2019 - Newly identified subset of immune cells may be key to fighting chronic inflammation
January 19, 2019 - New immune response regulators discovered
January 18, 2019 - Poor blood oxygenation during sleep predicts chance of heart-related death
January 18, 2019 - First international consensus on the diagnosis and management of fibromuscular dysplasia
January 18, 2019 - Rapid resistance gene sequencing technology can hasten identification of antibiotic-resistant bacteria
January 18, 2019 - Researchers develop artificial enzymatic pathway for synthesizing isoprenoids in E. coli
January 18, 2019 - Scientists advise caution in immunotherapy research
January 18, 2019 - How children across the world develop language
January 18, 2019 - Columbia Medical Student Receives McDonogh Scholarship
January 18, 2019 - Secretive ‘Rebate Trap’ Keeps Generic Drugs For Diabetes And Other Ills Out Of Reach
January 18, 2019 - Plant based diet could be the best option for the planet says commission
January 18, 2019 - New conservation practice could reduce nitrogen from agricultural drainage, study shows
January 18, 2019 - UIC researchers receive $1.7 million NCI grant to study Southeast Asian fruit
January 18, 2019 - New study determines the fate of DNA derived from genetically modified food
January 18, 2019 - Scientists develop new gene therapy that prevents axon destruction in mice
January 18, 2019 - Study finds critically low HPV vaccination rates among younger adolescents in the U.S.
January 18, 2019 - Brain cells involved in memory play key role in reducing future eating behavior
January 18, 2019 - Risk for Conversion of MS Varies With Different Therapies
January 18, 2019 - Investigational cream may help patients with inflammatory skin disease
January 18, 2019 - Medical school news office receives six writing awards | News Center
January 18, 2019 - County By County, Researchers Link Opioid Deaths To Drugmakers’ Marketing
January 18, 2019 - Research reveals risk for developing more than one mental health disorder
January 18, 2019 - Scientists discover a dramatic pattern of bone growth in female mice
January 18, 2019 - Study finds link between lengthy periods of undisturbed maternal sleep and stillbirths
January 18, 2019 - New nuclear medicine method could improve detection of primary and metastatic melanoma
January 18, 2019 - Combination therapy shows high efficacy in treating people with leishmaniasis and HIV
January 18, 2019 - Health Tip: Don’t Ignore Changes in Skin Color
January 18, 2019 - Dietary Recommendations for Healthy Children
January 18, 2019 - Eliminating the latent reservoir of HIV
January 18, 2019 - Pain From The Government Shutdown Spreads. This Time It’s Food Stamps
January 18, 2019 - Newly discovered regulatory mechanism helps control fat metabolism
January 18, 2019 - New rapid blood tests could speed up TB diagnosis, save the NHS money
January 18, 2019 - Researchers develop intelligent system for ‘tuning’ powered prosthetic knees
January 18, 2019 - Monoclonal antibody pembrolizumab prolongs survival in patients with squamous cell carcinoma
January 18, 2019 - Maintaining an active lifestyle in older age could prevent dementia
January 18, 2019 - New research detects mosquito known to transmit malaria for the first time in Ethiopia
January 18, 2019 - Researchers identify new genes linked to development of age-related macular degeneration
January 18, 2019 - Computerized method helps better protect pharma patents
January 18, 2019 - New guidelines to make swallowing safer for people in Australian nursing homes
January 18, 2019 - Lumex Instruments’ RA-915AM monitor installed at Hg treatment plant in Almadén, Spain
January 18, 2019 - ACCC survey finds multiple threats to growth of cancer programs
January 18, 2019 - Meeting the challenge of engaging men in HIV prevention and treatment
January 18, 2019 - Furloughed Feds’ Health Coverage Intact, But Shutdown Still Complicates Things
January 18, 2019 - Experts discuss various aspects on health risks posed by fumigated containers
January 18, 2019 - Researchers use gene-editing tool CRISPR/Cas9 to limit impact of parasitic diseases
January 18, 2019 - Alpha neurofeedback training could be a means of enhancing learning success
January 18, 2019 - Innovative ‘light’ method demonstrates positive results in fight against malignant tumors
January 18, 2019 - The cytoskeleton of neurons found to play role in Alzheimer’s disease
January 18, 2019 - New resource-based approach to improve HIV care in low- and middle-income countries
January 18, 2019 - Bedfont appoints Dr Jafar Jafari as first member of the Gastrolyzer Medical Advisory Board
Genomic study finds a new role for microRNAs as predictors of Crohn’s disease progression

Genomic study finds a new role for microRNAs as predictors of Crohn’s disease progression

image_pdfDownload PDFimage_print
High magnification micrograph of Crohn’s disease. Biopsy of esophagus. H&E stain. Credit: Nephron/Wikipedia

Crohn’s disease is a lifelong condition characterized by a fluctuating course of gastro-intestinal inflammation with repeated flares and remissions. Any part of the alimentary tract from the mouth to the anus can be affected resulting in diverse symptoms including abdominal pain, watery diarrhea, and hematochezia. Furthermore, persistent inflammation can result in complications, such as a narrowing of the large intestine called strictures or perforations in the intestinal wall, both of which often require surgical treatment and severely compromise the quality of life of Crohn’s patients. The incidence of Crohn’s disease has increased throughout the world over the last 50 years for all ages, indicating its emergence as a global disease.

Currently available drugs for Crohn’s disease also increase the potential risk of serious side effects including opportunistic infection and cancer development. Because disease course widely varies among patients and no “one size fits all” treatment exists, determining which patients are at high risk for poor clinical outcome is a critical problem in the management of Crohn’s disease.

Now a new study conducted in adult and pediatric patients with Crohn’s disease, led by UNC School of Medicine researchers and published in the Journal of Clinical Investigation (JCI) Insight, has found that a set of biomolecules known as microRNAs, specifically microRNA-31 (miR-31), can help predict which patients with Crohn’s disease are at higher risk for the development of severe problems that may require surgical removal of the large intestine.

“For 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, Ph.D., associate professor of medicine and genetics. “These 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.”

A key validation step in this research involved the generation of organoids or ‘mini-guts’ that architecturally and physiologically resemble the human intestine. Sheikh and colleagues derived organoids from Crohn’s patients to preserve the molecular defects observed in the patient tissue.

“This innovative system can serve as a personalized testing platform to screen therapeutic agents before administering them to the patient,” Sheikh said.”

In the study, small RNA-sequencing was performed on adult colon tissue from 18 adults with Crohn’s disease and 12 controls. Small RNA-sequencing was also performed on colon tissue from 76 children who were newly diagnosed with Crohn’s 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.

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.

“In recent years there has been great success in deriving molecular signatures that classify several cancers into subtypes, including studies performed here at UNC,” said co-senior author Terry Furey, Ph.D., associate professor of genetics and biology and a member of the UNC Lineberger Comprehensive Cancer Center. “These 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’s 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.”

The third co-corresponding author is Praveen Sethupathy, Ph.D., 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. “While 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’s disease and developing more personalized therapeutic strategies for patients. Also, our study emphasizes the importance of epithelial biology in Crohn’s disease, which merits deeper investigation to delineate mechanisms that underlie the etiology of different disease subtypes,” Sethupathy said.

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.

“Preserving tissue in this way usually results in heavily degraded mRNA,” Keith said. “But 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’s disease,” Keith said.


Explore further:
Researchers find two distinct genetic subtypes in Crohn’s disease patients

Journal reference:
Journal of Clinical Investigation

Provided by:
University of North Carolina Health Care

Tagged with:

About author

Related Articles