miR-375

CINCINNATI CHILDRENS HOSPITAL MEDICAL CENTER LOGOCINCINNATI, March 28, 2012 /PRNewswire-USNewswire/ — Researchers have taken a critical step in understanding how allergic reactions occur after identifying a genetic signature for regulation of a key immune hormone, interleukin (IL-13).

Scientists from Cincinnati Children’s Hospital Medical Center say the finding opens the potential for new molecular targets to treat allergic disease. They report on March 28 in Mucosal Immunology that a particular microRNA, miR-375, is regulated by IL-13, and in turns regulates how IL-13 induces pro-allergic changes, particularly in epithelial cells in the lung and esophagus.

The data support a role for miR-375 in asthma and in eosinophilic esophagitis (EoE), a severe, often painful food allergy that renders children unable to eat a wide variety of foods. EoE can also cause weight loss, vomiting, heartburn and swallowing difficulties.

“The identification of a microRNA that regulates IL-13-induced changes and inflammatory pathways is a significant advancement for the understanding and future treatment of allergic disease,” says Marc E. Rothenberg, MD, senior investigator on the study and director of the Division of Allergy and Immunology and Center for Eosinophilic Disorders at Cincinnati Children’s. “MiR-375 is proof of principle that microRNAs are involved in fine-tuning IL-13-mediated responses, which opens up a set of new possibilities for novel therapeutic targets for treatment of allergic disease.”

IL-13 induces changes in epithelial gene and protein expression that are important in the onset of many allergic diseases, including EoE. Notably, expression of miR-375 was consistently [click to continue…]

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CINCINNATI CHILDRENS HOSPITAL MEDICAL CENTER LOGOCINCINNATI, March 9, 2012 /PRNewswire-USNewswire/ – Researchers have identified a genetic signature for a severe, often painful food allergy – eosinophilic esophagitis – that could lead to improved diagnosis and treatment for children unable to eat a wide variety of foods.

The scientists, from Cincinnati Children’s Hospital Medical Center, report in the Journal of Allergy and Clinical Immunology that they have pinpointed a dysregulated microRNA signature for eosinophilic esophagitis (EoE), a disease that also may cause weight loss, vomiting, heartburn and swallowing difficulties.

Interestingly, the dysregulated microRNA was reversible with steroid treatment, according to the study’s senior investigator, Marc E. Rothenberg, MD, PhD, director of Allergy and Immunology and the Center for Eosinophilic Disorders at Cincinnati Children’s. MicroRNAs are short segments of RNA that can regulate whether genetic messengers (mRNAs) are degraded or translated into protein.

“The identification of biomarkers specific to EoE is a significant advancement for both the diagnosis and treatment of the disease,” explains Rothenberg. “The microRNA signature provides an opportunity for more precise analysis of esophageal biopsies.”

Rothenberg said children with EoE now undergo anesthesia and invasive endoscopy to diagnose and monitor the allergy. The ability to determine the presence and status of EoE with a noninvasive method, such as blood test that measures microRNAs, would have a positive impact on individuals and families.

In the current study, investigators analyzed esophageal microRNA expression of patients with active EoE, steroid-induced EoE remission, patients with chronic (non-eosinophilic) esophagitis and of healthy individuals. Additionally, they assessed plasma microRNA expression of patients with active EoE, remission of EoE remission and of healthy individuals.

The researchers found that EoE was associated with 32 differentially regulated microRNAs and distinguishable from the non-eosinophilic forms of esophagitis (such as reflux disease). Esophageal eosinophil levels correlated significantly with [click to continue…]

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Low-Level Expression of miR-375 Correlates with Poor Outcome and Metastasis While Altering the Invasive Properties of Head and Neck Squamous Cell Carcinomas.

Researchers at Department of Pathology, Albert Einstein College of Medicine used global miRNA expression profiling of head and neck squamous cell carcinoma (HNSCC) samples and adjacent normal tissue to rank those miRNAs that were most significantly altered in a patient population of 123. Harris et al. evaluated 736 of the currently known 1898 unique mature human microRNAs. Rank Consistency Score analysis revealed miR-375 to have the most significantly lowered miRNA levels in tumors relative to matched adjacent nonmalignant tissue from the same patient.

While this result has been previously observed by other groups, this latest study reveals that low miR-375 expression levels correlate significantly with cancer survival and distant metastasis. In a study of 123 primary HNSCC patients using multivariable Cox proportional hazard ratios (HR) and 95% confidence intervals (CI), both death from disease (HR: 12.8, 95% CI: 3 to 49) and incidence of distant metastasis (HR: 8.7, 95% CI: 2 to 31) correlated with lower expression levels of miR-375 regardless of the site or stage of the tumor. In addition, oral cavity tumor cell lines (eg, UMSCC1 and UMSCC47) overexpressing miR-375 were significantly less invasive in vitro than their matched empty vector controls.

The authors conclude that miR-375 may be suitable as a potential prognostic marker of poor outcome and metastasis in HNSCC and that it may function by suppressing the tumor’s invasive properties.

Harris T, Jimenez L, Kawachi N, Fan JB, Chen J, Belbin T, Ramnauth A, Loudig O, Keller CE, Smith R, Prystowsky MB, Schlecht NF, Segall JE, Childs G.
Low-Level Expression of miR-375 Correlates with Poor Outcome and Metastasis While Altering the Invasive Properties of Head and Neck Squamous Cell Carcinomas.
Am J Pathol., in press.

http://www.sciencedirect.com/science/article/pii/S0002944011010947

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