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MicroRNA-24 and Ulcerative Colitis: Expression, Functionality, and Therapeutic Potential

  • Author(s): Soroosh, Artin
  • Advisor(s): Pothoulakis, Charalabos
  • et al.
Abstract

Ulcerative Colitis is a chronic inflammatory disease of the gastrointestinal tract that affects over 1 million people in the United States resulting in $2.7 billion in healthcare costs each year. Ulcerative Colitis is characterized by chronic, uncontrolled inflammation localized to the colon and rectum which leads to debilitating symptoms and significant complications. This disease has limited treatment options, with 20-25% of patients needing surgical intervention to alleviate symptoms. Many researchers are focused on finding new therapeutic targets for Ulcerative Colitis to aid those patients for whom the current treatments are not effective. One potential target, microRNAs, are small, single-stranded RNAs with the ability to repress gene expression. Many microRNAs are implicated in the pathophysiology of different diseases, including Ulcerative Colitis. MicroRNA-24 is a specific microRNA that is associated with multiple cancers, cardiovascular disease, and inflammatory activity. Here, we describe the expression, function, and therapeutic potential for microRNA-24 in Ulcerative Colitis. Our data reveal that microRNA-24 is elevated in Ulcerative Colitis and disrupts intestinal barrier function by targeting the tight junction protein cingulin. Furthermore, microRNA-24 inhibition in mouse models of colitis impaired epithelial restitution during the recovery period. We discovered that microRNA-24 robustly regulates apoptosis in the intestinal epithelium. Consequently, microRNA-24 inhibition promoted cell death which hindered mucosal repair. Taken together, this work highlights microRNA-24 as a relevant factor in the pathogenesis of Ulcerative Colitis that deserves further study to unlock its utility as a therapeutic target.

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