Serrated adenocarcinoma (SAC) and colorectal carcinomas showing histological and molecular features of high-level of microsatellite instability (hmMSI-H) are both end points of the serrated pathway of colorectal carcinogenesis. Despite common features (right-sided location, CpG island methylation phenotype and BRAF mutation) there are no studies comparing the microRNA (miRNA) expression profiles in SACs and hmMSI-H. The microtranscriptome from 12 SACs and 8 hmMSI-H were analysed using Affymetrix GeneChip miRNA 3.0 arrays and differentially enriched functions involving immune response were observed from this comparison. miR-181a-2* was found significantly more expressed in hmMSI-H than in SAC and higher expression of this miRNA in microsatellite unstable colorectal cancer were corroborated by Real-Time PCR in an extended series (61 SAC, 21 hmMSI-H). An analysis of genes possibly regulated by miR-181a-2* was carried out and, amongst these, an inverse correlation of NAMPT with miR-181a-2* expression was observed, whereas, for TRAF1 and SALL1, additional regulation mechanisms involving CpG island methylation were observed. miR-181a-2* is associated with particular histological and molecular features of colorectal carcinomas within the serrated pathological pathway and might play a role in the immune responses of microsatellite instability carcinomas.

Biomedical Informatics and Bioinformatics Platform Institute for Bio health Research of Murcia Foundation for Healthcare Training and Research of the Region of Murcia Calle Luis Fontes Pagán 9 Murcia Spain

Central European Institute of Technology Masaryk University Brno Czech Republic

Clinical Analysis Department Santa Lucia University Hospital Cartagena Spain

Department of Histology and Pathology Faculty of Life Sciences Catholic University of Murcia Avda Los Jerónimos Murcia Spain

Department of Pathology University Hospital Brno Jihlavská 340 20 Brno Bohunice Brno Starý Lískovec Czech Republic

Department of Surgery University Hospital Brno Brno Bohunice Brno Starý Lískovec Czech Republic

Pathology Department Santa Lucia University Hospital Cartagena Spain

Research Group on Molecular Pathology and Pharmacogenetics Institute for Bio health Research of Murcia Santa Lucia University Hospital C Mezquita sn 30202 Cartagena Spain

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