An essential mesenchymal function for miR-143/145 in intestinal epithelial regeneration.

Downregulation of the miR-143/145 microRNA (miRNA) cluster has been repeatedly reported in colon cancer and other epithelial tumors. In addition, overexpression of these miRNAs inhibits tumorigenesis, leading to broad consensus that they function as cell-autonomous epithelial tumor suppressors. We generated mice with deletion of miR-143/145 to investigate the functions of these miRNAs in intestinal physiology and disease in vivo. Although intestinal development proceeded normally in the absence of these miRNAs, epithelial regeneration after injury was dramatically impaired. Surprisingly, we found that miR-143/145 are expressed and function exclusively within the mesenchymal compartment of intestine. Defective epithelial regeneration in miR-143/145-deficient mice resulted from the dysfunction of smooth muscle and myofibroblasts and was associated with derepression of the miR-143 target Igfbp5, which impaired IGF signaling after epithelial injury. These results provide important insights into the regulation of epithelial wound healing and argue against a cell-autonomous tumor suppressor role for miR-143/145 in colon cancer.

Tumor suppression by miR-26 overrides potential oncogenic activity in intestinal tumorigenesis.

Down-regulation of miR-26 family members has been implicated in the pathogenesis of multiple malignancies. In some settings, including glioma, however, miR-26-mediated repression of PTEN promotes tumorigenesis. To investigate the contexts in which the tumor suppressor versus oncogenic activity of miR-26 predominates in vivo, we generated miR-26a transgenic mice. Despite measureable repression of Pten, elevated miR-26a levels were not associated with malignancy in transgenic animals. We documented reduced miR-26 expression in human colorectal cancer and, accordingly, showed that miR-26a expression potently suppressed intestinal adenoma formation in Apc(min/+) mice, a model known to be sensitive to Pten dosage. These studies reveal a tumor suppressor role for miR-26 in intestinal cancer that overrides putative oncogenic activity, highlighting the therapeutic potential of miR-26 delivery to this tumor type.

Are you better off than you were 4 years ago? Measuring the impact of the ABS flexible endoscopy curriculum.

INTRODUCTION: In 2014, the ABS introduced the Flexible Endoscopy Curriculum (FEC). The FEC did not alter the minimum defined category case volumes for endoscopy; however, it did introduce specific cognitive and technical milestones for endoscopy training. It also mandated that residents pass the Fundamentals of Endoscopic Skills (FES) exam to qualify for board certification. Although significant research has been published regarding residents' success on the FES exam, very little is known regarding how the FEC has changed the way general surgery programs train their residents in surgical endoscopy. The aim of this study was to quantify changes in flexible endoscopy education at a large academic program in the 4 years since the FEC was published. METHODS: We classified the impact of FEC into four categories: (a) case volume or distribution, (b) clinical rotations, (c) required didactics or simulation exercises, and (d) FES pass rates. For category (a), we reviewed current and historical case logs for all categorical residents from 2013 to 2018. Mann-Whitney U tests were used to compare endoscopy volumes for each PGY level in 2013-2014 to the respective PGY level in 2017-2018 with p < 0.05 considered significant. For categories (b)-(d), we gathered historical records from the residency coordinator and endoscopy rotation director. RESULTS: Complete data were available for 57 residents in the 2013-2014 academic year and 56 residents in the 2017-2018 academic year. Median total endoscopies performed by PGY2, PGY3, and PGY5 residents all significantly increased during the FEC rollout. Our program's focus on endoscopy also expanded with absolute increases in endoscopy rotations, didactics, and simulation exercises. These changes translated into significantly increased pass rates on the FES exam from 40 to 100%. CONCLUSIONS: Implementation of the FEC at a large academic program led to measurable improvements in clinical experience, program structure, educational programing, and performance on high-stakes assessments.