Elovl5-KO Mouse

Elovl5, or Elongase of Very-Long Fatty Acid 5, is an enzyme that catalyzes fatty acid elongation, especially crucial for polyunsaturated fatty acid (PUFA) elongation [4,5,6,7,8,9]. It participates in lipid metabolism pathways, which are essential for maintaining normal membrane structure, embryonic lipid determination, and various physiological functions [4,5]. Genetic models, such as gene knockout mice, are valuable for studying its functions.

In prostate cancer, AR-mediated induction of ELOVL5 was demonstrated. ELOVL5 depletion suppressed prostate cancer cell proliferation, 3D growth, and in vivo tumor growth and metastasis, indicating its role in a protumorigenic metabolic pathway [1]. In breast cancer, downregulation of Elovl5 promoted metastasis through lipid-droplet accumulation-mediated induction of TGF-β receptors, and it was also a predictive biomarker of metastatic ER+ breast cancer [2]. In renal cell carcinoma, knockout of ELOVL5 suppressed cell proliferation, invasion, and in vivo tumor growth by affecting lipid droplet formation, apoptosis, and AKT-mTOR-STAT3 signaling [3]. In Elovl5 -/- mice, there were myelin structural alterations and reduced sciatic nerve conduction velocity, highlighting its role in the peripheral nervous system [4].

In conclusion, Elovl5 is essential for fatty acid elongation and lipid metabolism, playing a significant role in maintaining normal physiological functions. Model-based research, especially gene knockout models, has revealed its implications in cancer metastasis and nervous system function. Understanding Elovl5 provides insights into disease mechanisms and potential therapeutic targets in oncology and neurology.

References:

1. Centenera, Margaret M, Scott, Julia S, Machiels, Jelle, Swinnen, Johannes V, Butler, Lisa M. 2021. ELOVL5 Is a Critical and Targetable Fatty Acid Elongase in Prostate Cancer. In Cancer research, 81, 1704-1718. doi:10.1158/0008-5472.CAN-20-2511. https://pubmed.ncbi.nlm.nih.gov/33547161/

2. Kieu, Trinh-Le-Vi, Pierre, Léa, Derangère, Valentin, Ghiringhelli, François, Rialland, Mickaël. 2022. Downregulation of Elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of TGF-β receptors. In Cell death & disease, 13, 758. doi:10.1038/s41419-022-05209-6. https://pubmed.ncbi.nlm.nih.gov/36056008/

3. Nitta, Satoshi, Kandori, Shuya, Tanaka, Ken, Shimano, Hitoshi, Nishiyama, Hiroyuki. 2022. ELOVL5-mediated fatty acid elongation promotes cellular proliferation and invasion in renal cell carcinoma. In Cancer science, 113, 2738-2752. doi:10.1111/cas.15454. https://pubmed.ncbi.nlm.nih.gov/35670054/

4. Hoxha, Eriola, Balbo, Ilaria, Parolisi, Roberta, Caruso, Donatella, Tempia, Filippo. 2021. Elovl5 is required for proper action potential conduction along peripheral myelinated fibers. In Glia, 69, 2419-2428. doi:10.1002/glia.24048. https://pubmed.ncbi.nlm.nih.gov/34139039/

5. Lanzarini, Franciele, Pereira, Fernanda Alves, Camargo, Janine de, Mesquita, Fernando Silveira, Sudano, Mateus José. 2021. ELOVL5 Participates in Embryonic Lipid Determination of Cellular Membranes and Cytoplasmic Droplets. In International journal of molecular sciences, 22, . doi:10.3390/ijms22031311. https://pubmed.ncbi.nlm.nih.gov/33525659/

6. Balbo, Ilaria, Montarolo, Francesca, Boda, Enrica, Tempia, Filippo, Hoxha, Eriola. 2021. Elovl5 Expression in the Central Nervous System of the Adult Mouse. In Frontiers in neuroanatomy, 15, 669073. doi:10.3389/fnana.2021.669073. https://pubmed.ncbi.nlm.nih.gov/33994961/

7. Nikulin, Sergey, Razumovskaya, Alexandra, Poloznikov, Andrey, Alekseev, Boris, Tonevitsky, Alexander. 2023. ELOVL5 and IGFBP6 genes modulate sensitivity of breast cancer cells to ferroptosis. In Frontiers in molecular biosciences, 10, 1075704. doi:10.3389/fmolb.2023.1075704. https://pubmed.ncbi.nlm.nih.gov/36714261/

8. Wu, Guanlin, Zhang, Yan, Liang, Bo, Liu, Fang, Xu, Lina. 2024. miR-218-5p promotes hepatic lipogenesis through targeting Elovl5 in non-alcoholic fatty liver disease. In Biochemical pharmacology, 226, 116411. doi:10.1016/j.bcp.2024.116411. https://pubmed.ncbi.nlm.nih.gov/38972428/

9. Wu, Wenpeng, Ren, Tianying, Cao, Xiaojuan, Gao, Jian. 2023. Hepatic transcriptome analysis reveals that elovl5 deletion promotes PUFA biosynthesis and deposition. In Comparative biochemistry and physiology. Part D, Genomics & proteomics, 46, 101076. doi:10.1016/j.cbd.2023.101076. https://pubmed.ncbi.nlm.nih.gov/37080058/