Specific MicroRNA Pattern in Colon Tissue of Young Children with Eosinophilic Colitis

Abstract

Eosinophilic colitis (EC) is a common cause of haematochezia in infants and young children. The exact pathomechanism is not understood, and the diagnosis is challenging. The role of microRNAs as key class of regulators of mRNA expression and translation in patients with EC has not been explored. Therefore, the aim of the present study was to explore the miRNA profile in EC with respect to eosinophilic inflammation. Patients enrolled in the study (n = 10) had persistent rectal bleeding, and did not respond to elimination dietary treatment. High-throughput microRNA sequencing was carried out on colonic biopsy specimens of children with EC (EC: n = 4) and controls (C: n = 4) as a preliminary screening of the miRNA profile. Based on the next-generation sequencing (NGS) results and literature data, a potentially relevant panel of miRNAs were selected for further measurements by real-time reverse transcription (RT)-PCR (EC: n = 14, C: n = 10). Validation by RT-PCR resulted in significantly altered expression of miR-21, -31, -99b, -125a, -146a, -184, -221, -223, and -559 compared to controls (p ≤ 0.05). Elevation in miR-21, -99b, -146a, -221, and -223 showed statistically significant correlation to the extent of tissue eosinophilia. Based on our results, we conclude that the dysregulated miRNAs have a potential role in the regulation of apoptosis by targeting Protein kinase B/Mechanistic target of rapamycin (AKT/mTOR)-related pathways in inflammation by modulating Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related signalling and eosinophil cell recruitment and activation, mainly by regulating the expression of the chemoattractant eotaxin and the adhesion molecule CD44. Our results could serve as a basis for further extended research exploring the pathomechanism of EC.

MicroRNA-128 Confers Anti-Endothelial Adhesion and Anti-Migration Properties to Counteract Highly Metastatic Cervical Cancer Cells’ Migration in a Parallel-Plate Flow Chamber

“…MicroRNA-29a eliminates lung adenocarcinoma cells’ growth, migration, and invasion by targeting carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) [ 52 ]. Kiss et al reported a significant correlation between the expression changes of miR-99b and miR-221 and the number of tissue eosinophils in the colonic mucosa of eosinophilic colitis patients, which may strongly correlate with the inflammation of tissue eosinophilia [ 53 ]. MicroRNA-8 induces robust motor axon targeting by coordinated regulation of cell adhesion molecules (CAMs) during synapse development [ 54 ].…”

Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study

“…48 Interestingly, previous microRNA analysis of patients with EoC also suggested this phenomenon. 49 Furthermore, the dominance of caspase 3, in contrast to caspase 8 and the ripoptosome, further contrasts the tissue-specific responses related to EoC and EoE pathogenesis. 50 Our collective data suggest distinct molecular and cellular mechanisms are locally operational in patients with EoC.…”