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

• DOI: 10.1194/jlr.m076752
• Publication Date: 2017-10-26T17:05:11Z
• Authors: Silvia Cruz-Gil; Ruth Sanchez-Mart...; Marta Gomez de Ce...; Roberto Martin-He...; Teodoro Vargas; Susana Molina; Jesús Herranz; Alberto Davalos; Guillermo Reglero; Ana Ramirez de Mo...
• Keywords: 0301 basic medicine; micro-ribonucleic acid; lipid and lipoprotein metabolism; 0303 health sciences; invasiveness; Computational Biology; QD415-436; Lipid Metabolism; Biochemistry; 3. Good health; colorectal tumors; MicroRNAs; 03 medical and health sciences; patient relapse; 0302 clinical medicine; HEK293 Cells; Coenzyme A Ligases; Disease Progression; molecular biology; Humans; Colorectal Neoplasms; Cells, Cultured; Stearoyl-CoA Desaturase

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. Thirty-one 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 pro-tumorigenic 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 disease-free survival and a promising therapeutic miRNA in CRC.