Preoperative chemoradiotherapy for rectal cancer: the sensitizer role of the association between miR-375 and c-Myc

Abstract

// Raquel Conde-Muiño 1, * , Carlos Cano 2, * , Victoria Sánchez-Martín 3, 4 , Antonio Herrera 4, 5 , Ana Comino 1 , Pedro P. Medina 4, 5 , Pablo Palma 1, * and Marta Cuadros 3, 4, * 1 Division of Colon & Rectal Surgery, University Hospital Virgen de las Nieves, Granada, Spain 2 Department of Computer Science and Artificial Intelligence, University of Granada, Granada, Spain 3 Department of Biochemistry, Molecular Biology III and Immunology, University of Granada, Granada, Spain 4 GENYO, Centre for Genomics and Oncological Research, Pfizer/University of de Granada/Junta de Andalucía, PTS Granada, Granada, Spain 5 Department of Biochemistry and Molecular Biology I, University of Granada, Granada, Spain * These authors have contributed equally to this work Correspondence to: Marta Cuadros Celorrio, email: mcuadros@ugr.es Pedro Medina, email: pedro.medina@genyo.es Pablo Palma, email: pablopalma@andaluciajunta.es Keywords: regulatory networks, chemoradiotherapy-resistance, rectal cancer, miRNAs, c-Myc Received: April 21, 2017     Accepted: June 19, 2017     Published: July 19, 2017 ABSTRACT 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.