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

FERREYRA COMPAGNUCCI, M; POLO, B; CORREA, G; YANTORNO, M; MERCADER, MV; CHAVERO, P; DE MARÍA, J; ROCCA, A; ARRIOLA, J; SAMBUELLI, A.; NUEZ, G; MUGLIA C.I.; CURCIARELLO, R

Seattle

Congreso; ICMI2022; 2022

International Society Mucosal Immunology

MicroRNAs (miRNAs) are small and non-coding RNAs, whichinduce or repress target gene expression. Specific miRNAshave been associated with inflammatory bowel diseases (IBD)and/or colorectal cancer (CRC). Besides, mucosalmyofibroblasts are key stromal cells involved in IBDpathogenesis and in tumor microenvironment. We aimed to study whether there is differential expression of miR-21-5p andmiR-155-5p in the inflamed mucosa, and particularly inintestinal fibroblasts from IBD and CRC patients comparedwith healthy control intestinal mucosa, as potential earlybiomarkers for CRC. Total RNA was obtained from mucosalexplants from IBD patients, polyp and colon biopsies frompatients with CRC and healthy control patients. Intestinalfibroblasts were isolated from colon surgical pieces andprimary cultures were established. cDNA from biopsies and/orfibroblasts was obtained and miR-21-5p and miR-155-5pexpression was quantified by real- time qPCR with specificprimers. Target genes for these miRNAs, PDCD4 and CBX7,were also evaluated, along with TNF-α and TGF-β geneexpression. We detected higher expression levels of miR-21-5p in inflamed tissue compared to non-inflamed mucosa, andin tumor biopsies from CRC patients, whereas expression ofmiR-155-5p was variable among groups. The miR-21expression level correlated with its target gene expression, asPDCD4 was lower in inflamed tissue and fibroblasts comparedto healthy samples. Mucosal inflammation and fibroblastsactivity in IBD and CRC correlated with miR-21 increase.Further studies are underway, including fibroblasts RNA deepsequencing, to confirm that miR-21 and potentially othermiRNAs could be helpful to predict IBD outcomes to earlyprevent CRC onset.