Summary: Oleic acid, the main fatty acid in olive oil, can promote production of a molecule that suppresses tumor formation in brain cells.

Source: University of Edinburgh

Oleic Acid from Olive Oil May Block Molecular Steps That Lead to Brain Tumours

New laboratory research indicates that oleic acid — the principal fatty acid in olive oil — can interfere with molecular interactions that otherwise prevent the production of a tumour-suppressing microRNA in brain cells. The study, carried out by researchers at the University of Edinburgh, identifies a mechanism by which oleic acid supports the generation of miR-7, a small non-coding RNA known to inhibit tumour formation in brain tissue.

MicroRNAs (miRNAs) regulate gene expression and play a crucial role in controlling cell behaviour. miR-7 is enriched in the brain and has established tumour-suppressing activity. The Edinburgh team found that oleic acid helps restore miR-7 production by blocking a protein complex that normally suppresses its processing.

The protein at the centre of the study is Musashi homolog 2 (MSI2), which, together with Hu antigen R (HuR), can bind to the primary miR-7 transcript (pri‑miR‑7) and prevent its maturation into the active miR-7 molecule. Laboratory experiments showed that oleic acid prevents MSI2 and other RNA-binding proteins with RNA recognition motifs from stably binding the conserved terminal loop of pri‑miR‑7. By disrupting these protein–RNA interactions, oleic acid enables the cellular machinery to process pri‑miR‑7 into mature miR‑7, thereby promoting a molecular environment that can suppress tumorigenic pathways.

Researchers say it is too early to conclude that dietary olive oil prevents brain cancer, but the findings reveal a molecular effect of oleic acid that could guide future therapies. Image for illustrative purposes.

The team demonstrated these effects using human cell extracts and living cells cultured in the laboratory. Electrophoretic mobility shift assays in HeLa cell extracts showed that treatment with oleic acid disrupted pre-miR/protein complexes that normally block processing. In vitro processing assays confirmed that oleic acid rescued pri‑miR‑7 maturation that was otherwise inhibited by HuR and MSI2. Importantly, treatment with oleic acid increased levels of mature miR‑7 in HeLa cells, establishing a direct effect on miR‑7 biogenesis in cultured human cells.

Notably, the influence of oleic acid was selective: pri‑miR‑16 processing showed reduced efficiency in the presence of oleic acid, suggesting that oleic acid can remodel different pri‑miR/protein complexes in distinct ways. This selectivity highlights the potential for small molecules to differentially affect the biogenesis pathways of individual microRNAs.

While these findings reveal an intriguing molecular action of oleic acid, the researchers caution that laboratory results do not directly translate into dietary recommendations. Dr Gracjan Michlewski of the University of Edinburgh’s School of Biological Sciences, who led the study, said: “While we cannot yet say that olive oil in the diet helps prevent brain cancer, our findings do suggest that oleic acid can support the production of tumour-suppressing molecules in cells grown in the lab. Further studies could help determine the role that olive oil might have in brain health.”

About this research

Funding: Medical Research Council; Wellcome Trust.

Source / Contact: University of Edinburgh (press contact: Catriona Kelly)

Publication: The study appears in the Journal of Molecular Biology. Original research: “Oleic Acid Induces MiR-7 Processing through Remodeling of Pri‑MiR‑7/Protein Complex” by Santosh Kumar, Angela Downie Ruiz Velasco, and Gracjan Michlewski. Published online May 4, 2017. DOI: 10.1016/j.jmb.2017.05.001.

Abstract (summary of the original study)

MicroRNAs are tightly regulated at transcriptional and post-transcriptional levels; their maturation depends on interactions between primary miRNA transcripts (pri‑miRs), precursor-miRs (pre‑miRs) and specific RNA-binding proteins. HuR-mediated recruitment of MSI2 to the conserved terminal loop of pri‑miR‑7 reduces brain-enriched miR‑7 levels in a tissue-specific manner. The research shows that oleic acid (OA) inhibits binding of proteins containing RNA recognition motifs to the conserved terminal loop of pri‑miR‑7. Electrophoretic mobility shift assays in HeLa cell extracts demonstrated that OA disrupts pre‑miR/protein complexes. OA rescues in vitro processing of pri‑miR‑7 that is otherwise blocked by HuR and MSI2. Conversely, OA reduced processing of pri‑miR‑16, indicating OA may inhibit binding of other RRM-containing proteins required for miR‑16 maturation. Finally, OA treatment led to increased mature miR‑7 production in HeLa cells. Together, these results show that OA can regulate pri‑miR processing by remodeling their associated protein complexes, providing a tool for studying RNA processing and suggesting a potential lead for small molecules that target the miR‑7 biogenesis pathway.

Study citation: “Oleic Acid Induces MiR-7 Processing through Remodeling of Pri-MiR-7/Protein Complex” — Santosh Kumar, Angela Downie Ruiz Velasco, and Gracjan Michlewski. Journal of Molecular Biology. Published online May 4, 2017. DOI: 10.1016/j.jmb.2017.05.001.