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

Journal of Lipid Research
Silvia Cruz-GilAna Ramírez de Molina

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. 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.

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Citations

Jul 25, 2018·World Journal of Gastroenterology : WJG·Kenneth Kw ToWilliam Cs Cho
Jan 28, 2019·Lipids in Health and Disease·Alicja PakietAdriana Mika
Apr 23, 2020·Frontiers in Oncology·Ilias Georgakopoulos-SoaresApostolos Zaravinos
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Jul 3, 2021·Cancers·Paulína Pidíková, Iveta Herichová
Jul 3, 2021·International Journal of Molecular Sciences·Jiřina HofmanováJan Vondráček

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