Targeting the lipid metabolic axis ACSL/SCD in colorectal cancer progression by therapeutic miRNAs: MiR-19b-1 role

Abstract

An abnormal acyl-CoA synthetase/stearoyl-CoA desaturase (ACSL/SCD) lipid network fuels colon cancer progression, endowing cells with invasive and migratory properties. Therapies against this metabolic network may be useful to improve clinical outcomes. Because micro-RNAs (miRNAs/miRs) are important epigenetic regulators, we investigated novel miRNAs targeting this pro-Tumorigenic axis; hence to be used as therapeutic or prognostic miRNAs. Thirtyone putative common miRNAs were predicted to simultaneously target the three enzymes comprising the ACSL/SCD network. Target validation by quantitative RT-PCR, Western blotting, and luciferase assays showed miR-544a, miR-142, and miR-19b-1 as major regulators of the metabolic axis, ACSL/SCD. Importantly, lower miR-19b-1 expression was associated with a decreased survival rate in colorectal cancer (CRC) patients, accordingly with ACSL/SCD involvement in patient relapse. Finally, miR-19b-1 regulated the protumorigenic axis, ACSL/SCD, being able to inhibit invasion in colon cancer cells. Because its expression correlated with an increased survival rate in CRC patients, we propose miR-19b-1 as a potential noninvasive biomarker of diseasefree survival and a promising therapeutic miRNA in CRC.- Cruz-Gil, S., R. Sanchez-Martinez, M. Gomez de Cedron, R. Martin-Hernandez, T. Vargas, S. Molina, J. Herranz, A. Davalos, G. Reglero, and A. Ramirez de Molina. Targeting the lipid metabolic axis, ACSL/SCD, in colorectal cancer progression by therapeutic miRNAs: miR-19b-1 role.