Differential expression of miRNAs in IBD mucosa and intestinal fibroblasts: potential biomarkers for associated colorectal cancer

EMANUEL BARBIERA ROMERO; MALENA FERREYRA COMPAGNUCCI; MARÍA BELEN POLO; GUSTAVO J. CORREA; MARTÍN YANTORNO; MARIA VICTORIA MERCADER; PAULA CHAVERO; JULIO DE MARÍA; ANDRÉS ROCCA; JUAN ARRIOLA; ALICIA SAMBUELLI; GABRIEL NÚÑEZ; MARTÍN RUMBO; GUILLERMO HORACIO DOCENA; CECILIA ISABEL MUGLIA; RENATA CURCIARELLO

Seattle

Congreso; International Congress of Mucosal Immunology 2022; 2022

MicroRNAs (miRNAs) are small and non-codingRNAs, which induce or repress target gene expression. Specific miRNAs have beenassociated with inflammatory bowel diseases (IBD) and/or colorectal cancer (CRC).Besides, mucosal myofibroblasts are key stromal cells involved in IBDpathogenesis and in tumor microenvironment. Weaimed to study whether there is differential expression of miR-21-5p andmiR-155-5p in the inflamed mucosa, and particularly in intestinal fibroblastsfrom IBD and CRC patients compared with healthy control intestinal mucosa, aspotential early biomarkers for CRC.Total RNA was obtained from mucosalexplants from IBD patients, polyp and colon biopsies from patients with CRC andhealthy control patients. Intestinal fibroblasts were isolated from colonsurgical pieces and primary cultures were established. cDNA from biopsiesand/or fibroblasts was obtained and miR-21-5p and miR-155-5p expression wasquantified by real- time qPCR with specific primers. Target genes for thesemiRNAs, PDCD4 and CBX7, were also evaluated, along with TNF-α and TGF-β gene expression. We detected higher expression levelsof miR-21-5p in inflamed tissue compared to non-inflamed mucosa, and in tumorbiopsies from CRC patients, whereas expression of miR-155-5p was variable amonggroups. The miR-21 expression level correlated with its target gene expression,as PDCD4 was lower in inflamed tissue and fibroblasts compared to healthysamples. Mucosal inflammation and fibroblastsactivity in IBD and CRC correlated with miR-21 increase. Further studies areunderway, including fibroblasts RNA deep sequencing, to confirm that miR-21 and potentially other miRNAs could be helpfulto predict IBD outcomes to early prevent CRC onset.