The Inhibitory Role of miR-486-5p on CSC Phenotype Has Diagnostic and Prognostic Potential in Colorectal Cancer

SIMPLE SUMMARY: Colorectal cancer is nowadays one of the most diffuse cancers worldwide. Its early diagnosis is often linked with a positive outcome. However, colorectal cancer is a “silent” cancer and the first symptoms usually appear when this is already in an advanced stage. To this end, an improvement in diagnostic, prognostic methods is necessary. This scenario fits the present study, which through a multidisciplinary approach, involving the study of samples of human origins and in vitro studies, seeks to clarify the involvement of microRNAs in the regulation of cancer stem cells of colorectal cancer. The oncosuppressive role of miR-486-5p is here extensively investigated, supporting the hypothesis of its role in the biology of cancer stem cells, giving a contribution for further studies to investigate its possible use as a diagnostic and prognostic biomarker of colorectal cancer. ABSTRACT: Colorectal cancer (CRC) is the third most frequent cancer worldwide and the second cause of cancer deaths. Increasing evidences supports the idea that the poor prognosis of patients is related to the presence of cancer stem cells (CSCs), a cell population able to drive cancer recurrence and metastasis. The deregulation of microRNAs (miRNAs) plays a role in the formation of CSC. We investigated the role of hsa-miR-486-5p (miR-486-5p) in CRC, CSCs, and metastasis, in order to reach a better understanding of the biomolecular and epigenetic mechanisms mir-486-5p-related. The expression of miR-486-5p was investigated in three different matrices from CRC patients and controls and in CSCs obtained from the CRC cell lines HCT-116, HT-29, and T-84. In the human study, miR-486-5p was up-regulated in serum and stool of CRC patients in comparison with healthy controls but down-regulated in tumor tissue when compared with normal mucosa. miR-486-5p was also down-regulated in the sera of metastatic patients. In vitro, miR-486-5p was down-regulated in CSC models and it induced an inhibitory effect on stem factors and oncogenes in the main pathways of CSCs. Our results provide a step forward in understanding the role of mir-486-5p in CRC and CSC, and suggest that further studies are needed to investigate its diagnostic and prognostic power, possibly in combination with other biomarkers.