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.
Highlights
An abnormal acyl-CoA synthetase/stearoyl-CoA desaturase (ACSL/SCD) lipid network fuels colon cancer progression, endowing cells with invasive and migratory properties
Bioinformatics prediction of common miRNAs regulating the ACSL1/ACSL4/SCD pro-tumorigenic axis miRanda, PITA, TargetScan, and PICTAR5 were run in order to identify miRNA-gene interactions
A prediction was considered valid whenever it co-occurred in at least two algorithms; we identified 31 putative miRNAs (Fig. 1A) capable of targeting ACSL1, ACSL4, and SCD simultaneously
Summary
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. Lower miR-19b-1 expression was associated with a decreased survival rate in colorectal cancer (CRC) patients, with ACSL/SCD involvement in patient relapse. MiR-19b-1 regulated the protumorigenic axis, ACSL/SCD, being able to inhibit invasion in colon cancer cells. Targeting the lipid metabolic axis, ACSL/SCD, in colorectal cancer progression by therapeutic miRNAs: miR-19b-1 role. The ACSL/SCD lipid network fuels migratory and invasive properties through epithelial-mesenchymal transition (EMT) induction and is associated with an increased risk of relapse in CRC patients [5]. Micro-RNAs (miRNAs) are endogenous noncoding small RNAs that have recently emerged as potent epigenetic modulators, which bind to complementary regions within mRNAs to promote their degradation and/or
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
