Background & Aims Altered levels and functions of microRNAs (miRs) have been associated with inflammatory bowel diseases (IBDs), although little is known about their roles in pediatric IBD. We investigated whether colonic mucosal miRs are altered in children with ulcerative colitis (UC). Methods We used a library of 316 miRs to identify those that regulate phosphorylation of STAT3 in NCM460 human colonocytes incubated with interleukin-6. Levels of miR-124 were measured by real-time PCR analysis of colon biopsies from pediatric and adult patients with UC and patients without IBD (controls), and of HCT-116 colonocytes incubated with 5-aza-2’-deoxycytidine. Methylation of the MIR124 promoter was measured by quantitative methylation-specific PCR. Results Levels of phosphorylated STAT3 and the genes it regulates (encoding VEGF, BCL2, BCLXL, and MMP9) were increased in pediatric patients with UC, compared to control tissues. Overexpression of miR-124, let-7, miR-125, miR-26, or miR-101 reduced STAT3 phosphorylation by ≥75% in NCM460 cells; miR-124 had the greatest effect. miR-124 was downregulated specifically in colon tissues from pediatric patients with UC and directly targeted STAT3 mRNA. Levels of miR-124 were decreased whereas levels of STAT3 phosphorylation increased in colon tissues from pediatric patients with active UC, compared to those with inactive disease. Furthermore, levels of miR-124 and STAT3 were inversely correlated in mice with experimental colitis. Downregulation of miR-124 in tissues from children with UC was attributed to hypermethylation of its promoter region. Incubation of HCT-116 colonocytes with 5-aza-2’ deoxycytidine upregulated miR-124 and reduced levels of STAT3 mRNA. Conclusions MiR-124 appears to regulate the expression of STAT3. Reduced levels of miR-124 in colon tissues of children with active UC appear to increase expression and activity of STAT3, which could promote inflammation and pathogenesis of UC in children.

Professional identity formation (PIF) within medical education is the multifaceted, individualized process through which students develop new ways of being in becoming physicians. Personal backgrounds, values, expectations, interests, goals, relationships, and role models can all influence PIF and may account for diversity of both experience and the active constructive process of professional formation. Guided reflection, including reflective writing, has been used to enhance awareness and meaning making within the PIF process for both students and medical educators and to shed light on what aspects of medical education are most constructive for healthy PIF. Student voices about the PIF process now emerging in the literature are often considered and interpreted by medical educators within qualitative studies or in broad theoretical overviews of PIF.In this Commentary, the authors present a chorus of individual student voices from along the medical education trajectory. Medical students (years 1-4) and a first-year resident in pediatrics respond to a variety of questions based on prevalent PIF themes extracted from the literature to reflect on their personal experiences of PIF. Topics queried included pretending in medical education, role of relationships, impact of formal and informal curricula on PIF (valuable aspects as well as suggestions for change), and navigating and developing interprofessional relationships and identities. This work aims to vividly illustrate the diverse and personal forces at play in individual students' PIF processes and to encourage future pedagogic efforts supporting healthy, integrated PIF in medical education.