Differential expression of miRNAs in IBD intestinal mucosa and intestinal fibroblasts: in search of biomarkers for associated colorectal cáncer

BARBIERA EMANUEL; COMPAGNUCCI FERREYRA MALENA; POLO BELEN; CORREA GUSTAVO; YANTORNO MARTÍN; MERCADER MARIA; CHAVERO PAULA; DE MARIA JULIO; ROCCA ANDRES; ARRIOLA JUAN; SAMBUELLI ALICIA; NUÑEZ GABRIEL; RUMBO MARTÍN; DOCENA GUILLERMO; MUGLIA, CECILIA ISABEL; CURCIARELLO, RENATA

Conferencia; International Congress of Mucosal Immunology; 2023

MicroRNAs (miRNAs) are small and non-coding RNAs, which induce or repress target gene expression. Specific miRNAs have been associated with inflammatory bowel disease (IBD) and/or colorectal cancer (CRC). Besides, mucosal myofibroblasts are key stromal cells involved in IBD pathogenesis and in the tumor microenvironment. In this work, we aimed to study whether there is differential expression of miR-21-5p and miR-155-5p in inflamed mucosa, and particularly in intestinal fibroblasts, from IBD and or CRC patients, compared healthy control intestinal mucosa as potential early biomarkers for CRC.Total RNA was obtained from mucosal explants from IBD patients, healthy control patients, polyp biopsies and colon tumor biopsies. Intestinal fibroblasts were isolated from colon surgical pieces and primary cultures were established. cDNA from biopsies and/or fibroblasts was obtained and the miR-21-5p and miR-155-5p expression was quantified by real-time qPCR with specific primers. Target genes for these miRNAs, PDCD4 and CBX7, were also evaluated, along with TNF-α and TGF-β gene expression.We detected higher expression levels of miR-21-5p in inflamed tissue compared to non-inflamed mucosa and tumor biopsies from CRC patients, whereas expression of miR-155-5p was variable among groups. miR-21 expression levels correlate with its target genes expression, as PDCD4 was lower in inflamed tissue and fibroblasts compared to healthy samples. Further studies are underway and intestinal fibroblasts RNA deep sequencing is proposed to confirm that differential expression of these microRNAs and potentially other ones, could be useful to predict IBD outcome to early prevent CRC onset.