Preoperative chemoradiotherapy for rectal cancer: the sensitizer role of the association between miR-375 and c-Myc
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Raquel Conde-Muiño1,*, Carlos Cano2,*, Victoria Sánchez-Martín3,4, Antonio Herrera4,5, Ana Comino1, Pedro P. Medina4,5, Pablo Palma1,* and Marta Cuadros3,4,*
1Division of Colon & Rectal Surgery, University Hospital Virgen de las Nieves, Granada, Spain
2Department of Computer Science and Artificial Intelligence, University of Granada, Granada, Spain
3Department of Biochemistry, Molecular Biology III and Immunology, University of Granada, Granada, Spain
4GENYO, Centre for Genomics and Oncological Research, Pfizer/University of de Granada/Junta de Andalucía, PTS Granada, Granada, Spain
5Department of Biochemistry and Molecular Biology I, University of Granada, Granada, Spain
*These authors have contributed equally to this work
Marta Cuadros Celorrio, email: [email protected]
Pedro Medina, email: [email protected]
Pablo Palma, email: [email protected]
Keywords: regulatory networks, chemoradiotherapy-resistance, rectal cancer, miRNAs, c-Myc
Received: April 21, 2017 Accepted: June 19, 2017 Published: July 19, 2017
Administration of chemoradiation before tumor resection has revolutionized the management of locally advanced rectal cancer, but many patients have proven resistant to this preoperative therapy. Our group recently reported a negative correlation between c-Myc gene expression and this resistance. In the present study, integrated analysis of miRNA and mRNA expression profiles was conducted in 45 pre-treatment rectal tumors in order to analyze the expressions of miRNAs and c-Myc and their relationship with clinicopathological factors and patient survival. Twelve miRNAs were found to be differentially expressed by responders and non-responders to the chemoradiation. Functional classification revealed an association between the differentially expressed miRNAs and c-Myc. Quantitative real-time PCR results showed that miRNA-148 and miRNA-375 levels were both significantly lower in responders than in non-responders. Notably, a significant negative correlation was found between miRNA-375 expression and c-Myc expression. According to these findings, miRNA-375 and its targeted c-Myc may be useful as a predictive biomarker of the response to neoadjuvant treatment in patients with locally advanced rectal cancer.
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