News from the Journal of Lipid Research: a lotion inspired by babies’ skin, an inflammation-linked kinase and a cancer-fighting microRNA
miRNAs take the wrecking ball to colorectal cancer
Newswise — Many cancer cells have altered metabolism to enable rapid growth and carcinogenesis in the harsh tumor microenvironment. In a paper in the Journal of Lipid Research, researchers at the Madrid Institute of Advanced Studies (IMDEA) in Spain identify unique microRNA networks that may limit delivery of lipids to cancerous cells and help combat the disease. Ana Ramirez de Molina and her team, including first author Silvia Cruz Gil, work in the molecular oncology group at IMDEA’s Research Institute on Food and Health Sciences. The team previously identified a key pathway in altered lipid metabolism, known as the abnormal acyl-CoA synthetase/stearoyl-CoA desaturase, or ACSL/SCD, lipid network, which promotes invasion and migration of colorectal cancer cells. Inhibitors of the ACSL/SCD network reduce cancer cell viability. This network could present a novel colorectal cancer therapy target, so the group sought to identify inhibitory miRNAs.
Using bioinformatics, the researchers identified 31 miRNAs that might suppress expression of the ACSL/SCD network. They then confirmed the roles of miRNAs with RNA and protein detection techniques. They identified three major miRNAs that reduced both RNA and protein expression of ACSL/SCD: miR-544a, miR-142 and miR-19b. The group used cell invasion assays and biochemical techniques to show that miRNA-19b expression reduces cancer cell adhesion and invasion through direct targeting of the ACSL/SCD network. They also found that miRNA-19b expression reduced lipid storage and respiratory capacity. Treating patients with miRNAs like 19b potentially could provide targeted, tailored reduction of oncogene expression to reduce cancer progression. DOI: 10.1194/jlr.M076752
Babies’ skin inspires eczema lotion
Babies are soft and adorable and, as parents know, very delicate. Their skin must be moisturized frequently, because it is still slightly water-permeable. Newborns emerge from the womb covered with a waxy substance called the vernix, which protects their skin from drying. Recently, researchers have begun to realize that the vernix also helps babies adapt to life outside the womb by stimulating cells in the skin to make water-resistant lipid molecules. Scientists at Leiden University in the Netherlands, led by Joke Bouwstra, thought it might be possible to harness the vernix to treat adults with skin problems. They formulated a lotion based on lipids found in the vernix and tested it on the skin of healthy volunteers. In a recent paper in the Journal of Lipid Research, the researchers showed that disrupting the water barrier on healthy volunteers’ arms using tape caused a change in the lipids that make up the barrier. With the new, shorter-chain lipids, more water could escape through the damaged skin. Applying the lotion sped up recovery by returning the lipid profile to normal. The researchers found changes to the synthesis of lipids that were not included in the lotion, suggesting that the lotion could mimic the vernix by changing how the skin makes lipids. The researchers have not yet determined which ingredient drives the changes. The lotion, or one similar to it, might someday help treat itchy skin rashes like eczema that are driven by irritants crossing a broken skin barrier. DOI: 10.1194/jlr.M079186
How an inflammation-linked kinase binds the cell membrane
Sphingosine-1-phosphate is a phospholipid linked to cancer and inflammatory diseases including multiple sclerosis. The phospholipid is generated when sphingosine kinase 1, called SK1 for short, translocates to the plasma membrane and phosphorylates sphingosine, but the membrane recruitment step is not well-understood. In a new paper on the cover of the March issue of the Journal of Lipid Research, Michael Pulkoski-Gross and colleagues at Stony Brook University in New York identify a novel cationic patch near a known hydrophobic site on the enzyme, explaining its preference for anionic membrane lipids. Both the cationic and hydrophobic features, which form a single membrane-binding surface, are required for SK1 to bind to membranes and drive a cellular invasion phenotype that may be linked to cancer metastasis. The finding may offer a new target for drugs that disrupt the interface rather than the kinase active site. DOI: 10.1194/jlr.M081307
About the American Society for Biochemistry and Molecular Biology
The ASBMB is a nonprofit scientific and educational organization with more than 11,000 members worldwide. Most members teach and conduct research at colleges and universities. Others conduct research in government laboratories, at nonprofit research institutions and in industry. The Society publishes three journals: the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics. For more information about ASBMB, visit www.asbmb.org.
About the Journal of Lipid Research
The Journal of Lipid Research (JLR) is the most-cited journal devoted to lipids in the world. For over 50 years, it has focused on the science of lipids in health and disease. The JLR aims to be on the forefront of the emerging areas of genomics, proteomics, and lipidomics as they relate to lipid metabolism and function. For more information about JLR, visit www.jlr.org.