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

Andrea Pisano; Carmen Griñan-Lison; Cristiano Farace; Giovanni Fiorito; Grazia Fenu; Gema Jiménez; Fabrizio Scognamillo; Jesùs Peña-Martin; Alessio Naccarati; Johannes Pröll; Sabine Atzmüller; Barbara Pardini; Federico Attene; Gabriele Ibba; Maria Giuliana Solinas; David Bernhard; Juan Antonio Marchal; Roberto Madeddu

doi:10.3390/cancers12113432

Cancers (Nov 2020)

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

Andrea Pisano,
Carmen Griñan-Lison,
Cristiano Farace,
Giovanni Fiorito,
Grazia Fenu,
Gema Jiménez,
Fabrizio Scognamillo,
Jesùs Peña-Martin,
Alessio Naccarati,
Johannes Pröll,
Sabine Atzmüller,
Barbara Pardini,
Federico Attene,
Gabriele Ibba,
Maria Giuliana Solinas,
David Bernhard,
Juan Antonio Marchal,
Roberto Madeddu

Affiliations

Andrea Pisano: Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
Carmen Griñan-Lison: Centre for Biomedical Research (CIBM), Biopathology and Regenerative Medicine Institute (IBIMER), University of Granada, 18100 Granada, Spain
Cristiano Farace: Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
Giovanni Fiorito: Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
Grazia Fenu: Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
Gema Jiménez: Centre for Biomedical Research (CIBM), Biopathology and Regenerative Medicine Institute (IBIMER), University of Granada, 18100 Granada, Spain
Fabrizio Scognamillo: O.U. of Surgery I (Surgical Pathology), A.O.U. Sassari, 07100 Sassari, Italy
Jesùs Peña-Martin: Centre for Biomedical Research (CIBM), Biopathology and Regenerative Medicine Institute (IBIMER), University of Granada, 18100 Granada, Spain
Alessio Naccarati: Molecular Epidemiology and Exposome Research Unit, Italian Institute for Genomic Medicine (IIGM), c/o IRCCS Candiolo, Candiolo, 10060 Torino, Italy
Johannes Pröll: Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria
Sabine Atzmüller: Center for Medical Research, Johannes Kepler University, 4040 Linz, Austria
Barbara Pardini: Molecular Epidemiology and Exposome Research Unit, Italian Institute for Genomic Medicine (IIGM), c/o IRCCS Candiolo, Candiolo, 10060 Torino, Italy
Federico Attene: O.U. of Surgery I (Surgical Pathology), A.O.U. Sassari, 07100 Sassari, Italy
Gabriele Ibba: Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
Maria Giuliana Solinas: Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
David Bernhard: Division of Pathophysiology, Institute of Physiology and Pathophysiology, Medical Faculty, Johannes Kepler University, 4040 Linz, Austria
Juan Antonio Marchal: Centre for Biomedical Research (CIBM), Biopathology and Regenerative Medicine Institute (IBIMER), University of Granada, 18100 Granada, Spain
Roberto Madeddu: Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy

DOI: https://doi.org/10.3390/cancers12113432
Journal volume & issue: Vol. 12, no. 11
p. 3432

Abstract

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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.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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