Eci2, also known as enoyl-CoA δ-isomerase 2, is an enzyme involved in lipid metabolism [1,2,3,4,5,6,7]. It participates in fatty acid oxidation pathways, with its function being crucial for normal lipid metabolic processes in cells. The study of Eci2 in genetic models like knockout mice can provide insights into its role in biological processes and disease conditions [7].

In colorectal cancer, Eci2 has been shown to act as a tumor-suppressor gene. It reduces ether lipid-mediated Interleukin 8 (IL-8) expression, leading to decreased neutrophil recruitment and neutrophil extracellular traps formation. Mechanistically, Eci2 inhibits ether lipid production in CRC cells by inhibiting the peroxisomal localization of alkylglycerone phosphate synthase (AGPS) [1]. In the context of fatty acid oxidation, in Eci1-deficient fibroblasts, knockdown of Eci2 led to a more pronounced accumulation of C12:1 acylcarnitine on incubation with unsaturated fatty acids, suggesting Eci2 can compensate for Eci1 deficiency [7].

In conclusion, Eci2 plays essential roles in lipid metabolism-related biological functions. Through model-based research, especially in gene-knockout models, its tumor-suppressive role in colorectal cancer and its compensatory function in fatty acid oxidation have been revealed, providing valuable insights into related disease mechanisms.

References:

1. Chen, Lixia, Dai, Peiling, Liu, Lei, Yuan, Qinzi, Li, Xuenong. 2024. The lipid-metabolism enzyme ECI2 reduces neutrophil extracellular traps formation for colorectal cancer suppression. In Nature communications, 15, 7184. doi:10.1038/s41467-024-51489-1. https://pubmed.ncbi.nlm.nih.gov/39169021/

2. Park, Hee-Seon, Song, Ji-Won, Park, Jin-Ho, Won, Young-Suk, Kwon, Hyo-Jung. 2020. TXNIP/VDUP1 attenuates steatohepatitis via autophagy and fatty acid oxidation. In Autophagy, 17, 2549-2564. doi:10.1080/15548627.2020.1834711. https://pubmed.ncbi.nlm.nih.gov/33190588/

3. Dundr, Pavel, Bártů, Michaela, Hojný, Jan, Jirsová, Kateřina, Franková, Věra. 2020. HNF1B, EZH2 and ECI2 in prostate carcinoma. Molecular, immunohistochemical and clinico-pathological study. In Scientific reports, 10, 14365. doi:10.1038/s41598-020-71427-7. https://pubmed.ncbi.nlm.nih.gov/32873863/

4. Dan, Chao, Zhang, Haiyan, Zeng, Wenjing, Wang, Li, Yao, Qisheng. 2018. HNF1B expression regulates ECI2 gene expression, potentially serving a role in prostate cancer progression. In Oncology letters, 17, 1094-1100. doi:10.3892/ol.2018.9677. https://pubmed.ncbi.nlm.nih.gov/30655870/

5. Itkonen, Harri M, Brown, Michael, Urbanucci, Alfonso, Rekvig, Ole P, Mills, Ian G. . Lipid degradation promotes prostate cancer cell survival. In Oncotarget, 8, 38264-38275. doi:10.18632/oncotarget.16123. https://pubmed.ncbi.nlm.nih.gov/28415728/

6. Zhou, Li, Mei, Shuai, Ma, Xiaozhu, Ding, Hu, Yan, Jiangtao. 2024. Multi-omics insights into the pathogenesis of diabetic cardiomyopathy: epigenetic and metabolic profiles. In Epigenomics, 17, 33-48. doi:10.1080/17501911.2024.2435257. https://pubmed.ncbi.nlm.nih.gov/39623870/

7. van Weeghel, Michel, te Brinke, Heleen, van Lenthe, Henk, Hoppel, Charles L, Houten, Sander M. 2012. Functional redundancy of mitochondrial enoyl-CoA isomerases in the oxidation of unsaturated fatty acids. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 26, 4316-26. doi:10.1096/fj.12-206326. https://pubmed.ncbi.nlm.nih.gov/22782973/