Research Papers:

Deregulation of cancer-stem-cell-associated miRNAs in tissues and sera of colorectal cancer patients

Cristiano Farace, Andrea Pisano, Carmen Griñan-Lison, Giuliana Solinas, Gema Jiménez, Marina Serra, Esmeralda Carrillo, Fabrizio Scognamillo, Federico Attene, Andrea Montella, Juan Antonio Marchal _ and Roberto Madeddu _

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Oncotarget. 2020; 11:116-130. https://doi.org/10.18632/oncotarget.27411

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Cristiano Farace1,2,*, Andrea Pisano1,3,*, Carmen Griñan-Lison3,4,*, Giuliana Solinas1, Gema Jiménez3,4,5, Marina Serra1, Esmeralda Carrillo3,4,6, Fabrizio Scognamillo7, Federico Attene7, Andrea Montella1, Juan Antonio Marchal3,4,6,* and Roberto Madeddu1,2,*

1 Department of Biomedical Sciences, University of Sassari, Sassari, Italy

2 National Institute of Biostructures and Biosystems, Rome, Italy

3 Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, Granada, Spain

4 Instituto de Investigación Biosanitaria (ibs.Granada), Granada, Spain

5 Bio-Health Research Foundation of Eastern Andalusia - Alejandro Otero (FIBAO), Granada, Spain

6 Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain

7 O.U. of Surgery I (Surgical Pathology), A.O.U. Sassari, Sassari, Italy

* These authors contributed equally to this work

Correspondence to:

Roberto Madeddu,email: [email protected]
Juan Antonio Marchal,email: [email protected]

Keywords: colorectal cancer; metastasis; cancer stem cell; microRNA; biomarker

Received: October 18, 2019     Accepted: December 16, 2019     Published: January 14, 2020


Colorectal cancer (CRC) is a deadly tumour in Western countries characterized by high cellular/molecular heterogeneity. Cancer stem cells (CSC) act in cancer recurrence, drug-resistance and in metastatic epithelial-to-mesenchymal transition. microRNAs (miRNAs) contribute to cancer is increasing, and miRNA roles in CSC phenotype and fate and their utility as CRC biomarkers have also been reported. Here, we investigated miR-21, miR-221, miR-18a, miR-210, miR-31, miR-34a, miR-10b and miR-16 expression in experimental ALDH+ and CD44+/CD326+ colorectal CSCs obtained from the human CRC cell lines HCT-116, HT-29 and T-84. Then, we moved our analysis in cancer tissue (CT), healthy tissue (HT) and serum (S) of adult CRC patients (n=12), determining relationships with clinical parameters (age, sex, metastasis, biochemical serum markers). Specific miRNA patterns were evident in vitro (normal, monolayers and CSCs) and in patients’ samples stratified by TNM stage (LOW vs HIGH) or metastasis (Met vs no-Met). miR-21, miR-210, miR-34a upregulation ad miR-16 dowregulation associated with the CSCs phenotype. miR-31b robustly overexpressed in monolayers and CSCs, and in CT ad S of HIGH grade and Met patients, suggesting a role as marker of CRC progression and metastasis. miR-18a upregulated in all cancer models and associated to CSC phenotype, and to metastasis and age in patients. miR-10b downregulated in CT and S of LOW/HIGH grade and no-Met patients. Our results identify miRNAs useful as colorectal CSC biomarker and that miR-21, miR-210, miR-10b and miR-31b are promising markers of CRC. A specific role of miR-18a as metastatic CRC serum biomarker in adult patients was also highlighted.

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